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9  structures 377  species 1  interaction 1947  sequences 46  architectures

Family: Linker_histone (PF00538)

Summary: linker histone H1 and H5 family

Pfam includes annotations and additional family information from a range of different sources. These sources can be accessed via the tabs below.

This is the Wikipedia entry entitled "Histone". More...

Histone Edit Wikipedia article

Schematic representation of the assembly of the core histones into the nucleosome.

In biology, histones are highly alkaline proteins found in eukaryotic cell nuclei that package and order the DNA into structural units called nucleosomes.[1][2] They are the chief protein components of chromatin, acting as spools around which DNA winds, and play a role in gene regulation. Without histones, the unwound DNA in chromosomes would be very long (a length to width ratio of more than 10 million to 1 in human DNA). For example, each human cell has about 1.8 meters of DNA, but wound on the histones it has about 90 micrometers (0.09 mm) of chromatin, which, when duplicated and condensed during mitosis, result in about 120 micrometers of chromosomes.[3]

Core histone H2A/H2B/H3/H4
Protein H2AFJ PDB 1aoi.png
PDB rendering of Complex between nucleosome core particle (h3,h4,h2a,h2b) and 146 bp long DNA fragment based on 1aoi.
Identifiers
Symbol Histone
Pfam PF00125
Pfam clan CL0012
InterPro IPR007125
SCOP 1hio
SUPERFAMILY 1hio
linker histone H1 and H5 family
PBB Protein HIST1H1B image.jpg
PDB rendering of HIST1H1B based on 1ghc.
Identifiers
Symbol Linker_histone
Pfam PF00538
InterPro IPR005818
SMART SM00526
SCOP 1hst
SUPERFAMILY 1hst

Classes[edit]

Five major families of histones exist: H1/H5, H2A, H2B, H3 and H4.[2][4][5] Histones H2A, H2B, H3 and H4 are known as the core histones, while histones H1 and H5 are known as the linker histones.

Two of each of the core histones assemble to form one octameric nucleosome core (a solenoid (DNA)-like particle), and 147 base pairs of DNA wrap around this core particle 1.65 times in a left-handed super-helical turn.[6] The linker histone H1 binds the nucleosome at the entry and exit sites of the DNA, thus locking the DNA into place[7] and allowing the formation of higher order structure. The most basic such formation is the 10 nm fiber or beads on a string conformation. This involves the wrapping of DNA around nucleosomes with approximately 50 base pairs of DNA separating each pair of nucleosomes (also referred to as linker DNA). Higher-order structures include the 30 nm fiber (forming an irregular zigzag) and 100 nm fiber, these being the structures found in normal cells. During mitosis and meiosis, the condensed chromosomes are assembled through interactions between nucleosomes and other regulatory proteins.

The following is a list of human histone proteins:

Super family Family Subfamily Members
Linker
H1
H1F H1F0, H1FNT, H1FOO, H1FX
H1H1 HIST1H1A, HIST1H1B, HIST1H1C, HIST1H1D, HIST1H1E, HIST1H1T
Core
H2A
H2AF H2AFB1, H2AFB2, H2AFB3, H2AFJ, H2AFV, H2AFX, H2AFY, H2AFY2, H2AFZ
H2A1 HIST1H2AA, HIST1H2AB, HIST1H2AC, HIST1H2AD, HIST1H2AE, HIST1H2AG, HIST1H2AI, HIST1H2AJ, HIST1H2AK, HIST1H2AL, HIST1H2AM
H2A2 HIST2H2AA3, HIST2H2AC
H2B
H2BF H2BFM, H2BFS, H2BFWT
H2B1 HIST1H2BA, HIST1H2BB, HIST1H2BC, HIST1H2BD, HIST1H2BE, HIST1H2BF, HIST1H2BG, HIST1H2BH, HIST1H2BI, HIST1H2BJ, HIST1H2BK, HIST1H2BL, HIST1H2BM, HIST1H2BN, HIST1H2BO
H2B2 HIST2H2BE
H3
H3A1 HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J
H3A2 HIST2H3C
H3A3 HIST3H3
H4
H41 HIST1H4A, HIST1H4B, HIST1H4C, HIST1H4D, HIST1H4E, HIST1H4F, HIST1H4G, HIST1H4H, HIST1H4I, HIST1H4J, HIST1H4K, HIST1H4L
H44 HIST4H4

Structure[edit]

The nucleosome core is formed of two H2A-H2B dimers and a H3-H4 tetramer, forming two nearly symmetrical halves by tertiary structure (C2 symmetry; one macromolecule is the mirror image of the other).[6] The H2A-H2B dimers and H3-H4 tetramer also show pseudodyad symmetry. The 4 'core' histones (H2A, H2B, H3 and H4) are relatively similar in structure and are highly conserved through evolution, all featuring a 'helix turn helix turn helix' motif (which allows the easy dimerisation). They also share the feature of long 'tails' on one end of the amino acid structure - this being the location of post-translational modification (see below).

It has been proposed that histone proteins are evolutionarily related to the helical part of the extended AAA+ ATPase domain, the C-domain, and to the N-terminal substrate recognition domain of Clp/Hsp100 proteins. Despite the differences in their topology, these three folds share a homologous helix-strand-helix (HSH) motif.[8]


Using an electron paramagnetic resonance spin-labeling technique, British researchers measured the distances between the spools around which eukaryotic cells wind their DNA. They determined the spacings range from 59 to 70 Å.[9]

In all, histones make five types of interactions with DNA:

  • Helix-dipoles from alpha-helices in H2B, H3, and H4 cause a net positive charge to accumulate at the point of interaction with negatively charged phosphate groups on DNA
  • Hydrogen bonds between the DNA backbone and the amide group on the main chain of histone proteins
  • Nonpolar interactions between the histone and deoxyribose sugars on DNA
  • Salt bridges and hydrogen bonds between side chains of basic amino acids (especially lysine and arginine) and phosphate oxygens on DNA
  • Non-specific minor groove insertions of the H3 and H2B N-terminal tails into two minor grooves each on the DNA molecule

The highly basic nature of histones, aside from facilitating DNA-histone interactions, contributes to their water solubility.

Histones are subject to post translational modification by enzymes primarily on their N-terminal tails, but also in their globular domains[citation needed]. Such modifications include methylation, citrullination, acetylation, phosphorylation, SUMOylation, ubiquitination, and ADP-ribosylation. This affects their function of gene regulation (see functions).

In general, genes that are active have less bound histone, while inactive genes are highly associated with histones during interphase[citation needed]. It also appears that the structure of histones has been evolutionarily conserved, as any deleterious mutations would be severely maladaptive. All histones have a highly positively charged N-terminus with many lysine and arginine residues.

History[edit]

Histones were discovered in 1884 by Albrecht Kossel. The word "histone" dates from the late 19th century and is from the German "Histon", of uncertain origin: perhaps from Greek histanai or from histos. Until the early 1990s, histones were dismissed by most as inert packing material for eukaryotic nuclear DNA, based in part on the "ball and stick" models of Mark Ptashne and others who believed that transcription was activated by protein-DNA and protein-protein interactions on largely naked DNA templates, as is the case in bacteria. During the 1980s, work by Michael Grunstein[10] demonstrated that eukaryotic histones repress gene transcription, and that the function of transcriptional activators is to overcome this repression. It is now known that histones play both positive and negative roles in gene expression, forming the basis of the histone code.

The discovery of the H5 histone appears to date back to 1970s,[11][12] and in classification it has been grouped with H1.[2][4][5]

Conservation across species[edit]

Histones are found in the nuclei of eukaryotic cells, and in certain Archaea, namely Euryarchaea, but not in bacteria. The unicellular algae known as dinoflagellates are the only eukaryotes that are known to completely lack histones.[13]

Archaeal histones may well resemble the evolutionary precursors to eukaryotic histones. Histone proteins are among the most highly conserved proteins in eukaryotes, emphasizing their important role in the biology of the nucleus.[2]:939 In contrast mature sperm cells largely use protamines to package their genomic DNA, most likely because this allows them to achieve an even higher packaging ratio.[14]

Core histones are highly conserved proteins; that is, there are very few differences among the amino acid sequences of the histone proteins of different species. Linker histone usually has more than one form within a species and is also less conserved than the core histones.[citation needed]

There are some variant forms in some of the major classes. They share amino acid sequence homology and core structural similarity to a specific class of major histones but also have their own feature that is distinct from the major histones. These minor histones usually carry out specific functions of the chromatin metabolism. For example, histone H3-like CenpA is a histone associated with only the centromere region of the chromosome. Histone H2A variant H2A.Z is associated with the promoters of actively transcribed genes and also involved in the prevention of the spread of silent heterochromatin.[15] Furthermore, H2A.Z has roles in chromatin for genome stability.[16] Another H2A variant H2A.X binds to the DNA with double-strand breaks and marks the region undergoing DNA repair.[17] Histone H3.3 is associated with the body of actively transcribed genes.[18]

Function[edit]

Compacting DNA strands[edit]

Histones act as spools around which DNA winds. This enables the compaction necessary to fit the large genomes of eukaryotes inside cell nuclei: the compacted molecule is 40,000 times shorter than an unpacked molecule.

Chromatin regulation[edit]

Histones undergo posttranslational modifications that alter their interaction with DNA and nuclear proteins. The H3 and H4 histones have long tails protruding from the nucleosome, which can be covalently modified at several places. Modifications of the tail include methylation, acetylation, phosphorylation, ubiquitination, SUMOylation, citrullination, and ADP-ribosylation. The core of the histones H2A, H2B, and H3 can also be modified. Combinations of modifications are thought to constitute a code, the so-called "histone code".[19][20] Histone modifications act in diverse biological processes such as gene regulation, DNA repair, chromosome condensation (mitosis) and spermatogenesis (meiosis).[21]

The common nomenclature of histone modifications is:

  • The name of the histone (e.g., H3)
  • The single-letter amino acid abbreviation (e.g., K for Lysine) and the amino acid position in the protein
  • The type of modification (Me: methyl, P: phosphate, Ac: acetyl, Ub: ubiquitin)
  • The number of modifications (only Me is known to occur in more than one copy per residue. 1, 2 or 3 is mono-, di- or tri-methylation)

So H3K4me1 denotes the monomethylation of the 4th residue (a lysine) from the start (i.e., the N-terminal) of the H3 protein.

Examples of histone modifications in transcription regulation include:

Type of
modification
Histone
H3K4 H3K9 H3K14 H3K27 H3K79 H3K36 H4K20 H2BK5
mono-methylation activation[22] activation[23] activation[23] activation[23][24] activation[23] activation[23]
di-methylation repression[25] repression[25] activation[24]
tri-methylation activation[26] repression[23] repression[23] activation,[24]
repression[23]
activation repression[25]
acetylation activation[26] activation[26] activation[27]

Functions of histone modifications[edit]

A huge catalogue of histone modifications have been described, but a functional understanding of most is still lacking. Collectively, it is thought that histone modifications may underlie a histone code, whereby combinations of histone modifications have specific meanings. However, most functional data concerns individual prominent histone modifications that are biochemically amenable to detailed study.

Chemistry of histone modifications[edit]

Methyl lysine.tif
  • Lysine methylation

The addition of one, two or three methyl groups to lysine has little effect on the chemistry of the histone; methylation leaves the charge of the lysine intact and adds a minimal number of atoms so steric interactions are mostly unaffected. However, proteins containing Tudor, chromo or PHD domains, amongst others, can recognise lysine methylation with exquisite sensitivity and differentiate mono, di and tri-methyl lysine, to the extent that, for some lysines (e.g.: H4K20) mono, di and tri-methylation appear to have different meanings. Because of this, lysine methylation tends to be a very informative mark and dominates the known histone modification functions.

Methyl arginine.tif
  • Arginine methylation

What was said above of the chemistry of lysine methylation also applies to arginine methylation, and some protein domains—e.g., Tudor domains—can be specific for methyl arginine instead of methyl lysine. Arginine is known to be mono- or di-methylated, and methylation can be symmetric or asymmetric, potentially with different meanings.

Acetyl lysine.tif
  • Lysine acetylation

Addition of an acetyl group has a major chemical effect on lysine as it neutralises the positive charge. This reduces electrostatic attraction between the histone and the negatively charged DNA backbone, loosening the chromatin structure; highly acetylated histones form more accessible chromatin and tend to be associated with active transcription. Lysine acetylation appears to be less precise in meaning than methylation, in that histone acetyltransferases tend to act on more than one lysine; presumably this reflects the need to alter multiple lysines to have a significant effect on chromatin structure.

Amino acid phosphorylations.tif
  • Serine/Threonine/Tyrosine phosphorylation

Addition of a negatively charge phosphate group can lead to major changes in protein structure, leading to the well-characterised role of phosphorylation in controlling protein function. It is not clear what structural implications histone phosphorylation has, but histone phosphorylation has clear functions as a post-translational modification, and binding domains such as BRCT have been characterised.

Functions in transcription[edit]

Most well-studied histone modifications are involved in control of transcription.

Actively transcribed genes[edit]

Two histone modifications are particularly associated with active transcription:

  • Trimethylation of H3 lysine 4 (H3K4Me3) at the promoter of active genes[28][29][30]

H3K4 trimethylation is performed by the COMPASS complex.[31][32][33] Despite the conservation of this complex and histone modification from yeast to mammals, it is not entirely clear what role this modification plays. However, it is an excellent mark of active promoters and the level of this histone modification at a gene’s promoter is broadly correlated with transcriptional activity of the gene. The formation of this mark is tied to transcription in a rather convoluted manner: early in transcription of a gene, RNA polymerase II undergoes a switch from initiating’ to ‘elongating’, marked by a change in the phosphorylation states of the RNA polymerase II C terminal domain (CTD). The same enzyme that phosphorylates the CTD also phosphorylates the Rad6 complex,[34][35] which in turn adds a ubiquitin mark to H2B K123 (K120 in mammals).[36] H2BK123Ub occurs throughout transcribed regions, but this mark is required for COMPASS to trimethylate H3K4 at promoters.[37][38]

  • Trimethylation of H3 lysine 36 (H3K36Me3) in the body of active genes

H3K36 trimethylation is deposited by the methyltransferase Set2.[39] This protein associates with elongating RNA polymerase II, and H3K36Me3 is indicative of actively transcribed genes.[40] H3K36Me3 is recognised by the Rpd3 histone deacetylase complex, which removes acetyl modifications from surrounding histones, increasing chromatin compaction and repressing spurious transcription.[41][42][43] Increased chromatin compaction prevents transcription factors from accessing DNA, and reduces the likelihood of new transcription events being initiated within the body of the gene. This process therefore helps ensure that transcription is not interrupted.

Repressed genes[edit]

Three histone modifications are particularly associated with repressed genes:

  • Trimethylation of H3 lysine 27 (H3K27Me3)

This histone modification is depositied by the polycomb complex PRC2.[44] It is a clear marker of gene repression,[45] and is likely bound by other proteins to exert a repressive function. Another polycomb complex, PRC1, can bind H3K27Me3[45] and adds the histone modification H2AK119Ub which aids chromatin compaction.[46][47] Based on this data it appears that PRC1 is recruited through the action of PRC2, however, recent studies show that PRC1 is recruited to the same sites in the absence of PRC2.[48][49]

  • Di and tri-methylation of H3 lysine 9 (H3K9Me2/3)

H3K9Me2/3 is a well-characterised marker for heterochromatin, and is therefore strongly associated with gene repression. The formation of heterochromatin has been best studied in the yeast Schizosaccharomyces pombe, where it is initiated by recruitment of the RNA-induced transcriptional silencing complex to double stranded RNAs produced from centromeric repeats.[50] RITS recruits the Clr4 histone methyltransferase which deposits H3K9Me2/3.[51] This process is called histone methylation. H3K9Me2/3 serves as a binding site for the recruitment of Swi6 (heterochromatin protein 1 or HP1, another classic heterochromatin marker)[52][53] which in turn recruits further repressive activities including histone modifiers such as histone deacetylases and histone methyltransferases.

  • Trimethylation of H4 lysine 20 (H4K20Me3)

This modification is tightly associated with heterochromatin,[54][55] although its functional importance remains unclear. This mark is placed by the Suv4-20h methyltransferase, which is at least in part recruited by heterochromatin protein 1.[54]

Bivalent promoters[edit]

Analysis of histone modifications in embryonic stem cells (and other stem cells) revealed many gene promoters carrying both H3K4Me3 and H3K27Me3, in other words these promoters display both activating and repressing marks simultaneously. This peculiar combination of modifications marks genes that are poised for transcription; they are not required in stem cells, but are rapidly required after differentiation into some lineages. Once the cell starts to differentiate, these bivalent promoters are resolved to either active or repressive states depending on the chosen lineage.[56]

Other functions[edit]

DNA damage[edit]

  • Phosphorylation of Histone H2AX at Serine 139

Phosphorylated H2AX (also known as gamma H2AX) is a marker for DNA double strand breaks,[57] and forms part of the response to DNA damage.[17][58] H2AX is phosphorylated early after detection of DNA double strand break, and forms a domain extending many kilobases either side of the damage.[57][59][60] Gamma H2AX acts as a binding site for the protein MDC1, which in turn recruits key DNA repair proteins[61] (this complex topic is well reviewed in[62]) and as such, gamma H2AX forms a vital part of the machinery that ensures genome stability.

  • Acetylation of H3 lysine 56 (H3K56Ac)

H3K56Acx is required for genome stability.[63][64] H3K56 is acetylated by the p300/Rtt109 complex,[65][66][67] but is rapidly deacetylated around sites of DNA damage. H3K56 acetylation is also required to stabilise stalled replication forks, preventing dangerous replication fork collapses.[68][69] Although in general mammals make far greater use of histone modifications than microorganisms, a major role of H3K56Ac in DNA replication exists only in fungi, and this has become a target for antibiotic development.[70]

See also[edit]

References[edit]

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External links[edit]

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This is the Wikipedia entry entitled "Histone H1". More...

Histone H1 Edit Wikipedia article

linker histone H1 and H5 family
PBB Protein HIST1H1B image.jpg
PDB rendering of HIST1H1B based on 1ghc.
Identifiers
Symbol Linker_histone
Pfam PF00538
InterPro IPR005818
SMART SM00526
SCOP 1hst
SUPERFAMILY 1hst

Histone H1 is one of the five main histone protein families which are components of chromatin in eukaryotic cells. Though highly conserved, it is nevertheless the most variable histone in sequence across species.

Structure[edit]

A cartoon showing where H1 can be found in the nucleosome

Metazoan H1 proteins feature a central globular domain and long C- and short N-terminal tails. H1 is involved with the packing of the "beads on a string" sub-structures into a high order structure, whose details have not yet been solved.[1]

Function[edit]

Unlike the other histones, H1 does not make up the nucleosome "bead". Instead, it sits on top of the structure, keeping in place the DNA that has wrapped around the nucleosome. H1 is present in half the amount of the other four histones, which contribute two molecules to each nucleosome bead. In addition to binding to the nucleosome, the H1 protein binds to the "linker DNA" (approximately 20-80 nucleotides in length) region between nucleosomes, helping stabilize the zig-zagged 30 nm chromatin fiber.[2] Much has been learned about histone H1 from studies on purified chromatin fibers. Ionic extraction of linker histones from native or reconstituted chromatin promotes its unfolding under hypotonic conditions from fibers of 30 nm width to beads-on-a-string nucleosome arrays.[3][4][5]

It is uncertain whether H1 promotes a solenoid (DNA)-like chromatin fiber, in which exposed linker DNA is shortened, or whether it merely promotes a change in the angle of adjacent nucleosomes, without affecting linker length.[6] Nuclease digestion and DNA footprinting experiments suggest that the globular domain of histone H1 localizes near the nucleosome dyad, where it protects approximately 15-30 base pairs of additional DNA.[7][8][9][10]

In addition, experiments on reconstituted chromatin reveal a characteristic stem motif at the dyad in the presence of H1.[11] Despite gaps in our understanding, a general model has emerged wherein H1’s globular domain closes the nucleosome by crosslinking incoming and outgoing DNA, while the tail binds to linker DNA and neutralizes its negative charge.[6][9]

Many experiments addressing H1 function have been performed on purified, processed chromatin under low-salt conditions, but H1’s role in vivo is less certain. Cellular studies have shown that overexpression of H1 can cause aberrant nuclear morphology and chromatin structure, and that H1 can serve as both a positive and negative regulator of transcription, depending on the gene.[12][13][14] In Xenopus egg extracts, linker histone depletion causes ~2-fold lengthwise extension of mitotic chromosomes, while overexpression causes chromosomes to hypercompact into an inseparable mass.[15][16] Complete knockout of H1 in vivo has not been achieved in multicellular organisms due to the existence of multiple isoforms that may be present in several gene clusters, but various linker histone isoforms have been depleted to varying degrees in Tetrahymena, C. elegans, Arabidopsis, fruit fly, and mouse, resulting in various organism-specific defects in nuclear morphology, chromatin structure, DNA methylation, and/or specific gene expression.[17][18][19]

Dynamics[edit]

A major surprise was the recent discovery from photobleaching experiments that linker histones to be a far more dynamic component of chromatin than core histones, with FRAP studies yielding a t50 of about 1 minute in somatic nuclei.[20][21]

It is difficult to understand how such a dynamic protein could be a structural component of chromatin, but it has been suggested that the steady-state equilibrium within the nucleus still strongly favors association between H1 and chromatin, meaning that despite its dynamics, the vast majority of H1 at any given timepoint is chromatin bound.[22] H1 compacts and stabilizes DNA under force and during chromatin assembly, which suggests that dynamic binding of H1 may provide protection for DNA in situations where nucleosomes need to be removed.[23]

Cytoplasmic factors appear to be necessary for the dynamic exchange of histone H1 on chromatin, but these have yet to be specifically identified.[24] H1 dynamics may be mediated to some degree by O-glycosylation and phosphorylation. O-glycosylation of H1 may promote chromatin condensation and compaction. Phosphorylation during interphase has been shown to decrease H1 affinity for chromatin and may promote chromatin decondensation and active transcription. However, during mitosis phosphorylation has been shown to increase the affinity of H1 for chromosomes and therefore promote mitotic chromosome condensation (see Mitotic Phosphorylation by CDK1).[16]

Isoforms[edit]

The H1 family in animals includes multiple H1 isoforms that can be expressed in different or overlapping tissues and developmental stages within a single organism. The reason for these multiple isoforms remains unclear, but both their evolutionary conservation from sea urchin to humans as well as significant differences in their amino acid sequences suggest that they are not functionally equivalent.[25][26][27] One isoform is histone H5, which is only found in avian erythrocytes, which unlike mammalian erythrocytes, have nuclei. Another isoform is the oocyte/zygotic H1M isoform (also known as B4 or H1foo), found in sea urchins, frogs, mice, and humans, which is replaced in the embryo by somatic isoforms H1A-E, and H10 which resembles H5.[27][28][29][30] Despite having more negative charges than somatic isoforms, H1M binds with higher affinity to mitotic chromosomes in Xenopus egg extracts.[16]

Mitotic Phosphorylation by CDK1[edit]

At mitosis, somatic H1 isoforms undergo phosphorylation at multiple cyclin-dependent kinase 1 (CDK1) consensus sites, which introduces multiple negative charges. Phosphorylation increases the affinity of H1 for mitotic chromosomes in Xenopus egg extracts and embryos, as determined by fluorescence recovery after photobleaching of wild-type H1 versus non-phosphorylable and phosphomimetic point mutants. These increases in binding affinity appear to offset the cytoplasmic dilution of H1 which occurs in mitotic cells following nuclear envelope breakdown, illustrating how the cell can regulate H1 to suit specific cellular conditions.[16]

See also[edit]

References[edit]

  1. ^ Ramakrishnan V, Finch JT, Graziano V, Lee PL, Sweet RM (March 1993). "Crystal structure of globular domain of histone H5 and its implications for nucleosome binding". Nature 362 (6417): 219–23. doi:10.1038/362219a0. PMID 8384699. 
  2. ^ Jeon, Kwang W.; Berezney, Ronald (1995). Structural and functional organization of the nuclear matrix. Boston: Academic Press. pp. 214–7. ISBN 0-12-364565-4. 
  3. ^ Finch JT, Klug A (June 1976). "Solenoidal model for superstructure in chromatin". Proc. Natl. Acad. Sci. U.S.A. 73 (6): 1897–901. doi:10.1073/pnas.73.6.1897. PMC 430414. PMID 1064861. 
  4. ^ Thoma F, Koller T (September 1977). "Influence of histone H1 on chromatin structure". Cell 12 (1): 101–7. doi:10.1016/0092-8674(77)90188-X. PMID 561660. 
  5. ^ Thoma F, Koller T, Klug A (November 1979). "Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin". J. Cell Biol. 83 (2 Pt 1): 403–27. doi:10.1083/jcb.83.2.403. PMC 2111545. PMID 387806. 
  6. ^ a b van Holde K, Zlatanova J (October 1996). "What determines the folding of the chromatin fiber?". Proc. Natl. Acad. Sci. U.S.A. 93 (20): 10548–55. doi:10.1073/pnas.93.20.10548. PMC 38190. PMID 8855215. 
  7. ^ Varshavsky AJ, Bakayev VV, Georgiev GP (February 1976). "Heterogeneity of chromatin subunits in vitro and location of histone H1". Nucleic Acids Res. 3 (2): 477–92. doi:10.1093/nar/3.2.477. PMC 342917. PMID 1257057. 
  8. ^ Whitlock JP, Simpson RT (July 1976). "Removal of histone H1 exposes a fifty base pair DNA segment between nucleosomes". Biochemistry 15 (15): 3307–14. doi:10.1021/bi00660a022. PMID 952859. 
  9. ^ a b Allan J, Hartman PG, Crane-Robinson C, Aviles FX (December 1980). "The structure of histone H1 and its location in chromatin". Nature 288 (5792): 675–9. doi:10.1038/288675a0. PMID 7453800. 
  10. ^ Staynov DZ, Crane-Robinson C (December 1988). "Footprinting of linker histones H5 and H1 on the nucleosome". EMBO J. 7 (12): 3685–91. PMC 454941. PMID 3208745. 
  11. ^ Bednar J, Horowitz RA, Grigoryev SA, Carruthers LM, Hansen JC, Koster AJ, Woodcock CL (November 1998). "Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin". Proc. Natl. Acad. Sci. U.S.A. 95 (24): 14173–8. doi:10.1073/pnas.95.24.14173. PMC 24346. PMID 9826673. 
  12. ^ Dworkin-Rastl E, Kandolf H, Smith RC (February 1994). "The maternal histone H1 variant, H1M (B4 protein), is the predominant H1 histone in Xenopus pregastrula embryos". Dev. Biol. 161 (2): 425–39. doi:10.1006/dbio.1994.1042. PMID 8313993. 
  13. ^ Brown DT, Alexander BT, Sittman DB (February 1996). "Differential effect of H1 variant overexpression on cell cycle progression and gene expression". Nucleic Acids Res. 24 (3): 486–93. doi:10.1093/nar/24.3.486. PMC 145659. PMID 8602362. 
  14. ^ Gunjan A, Alexander BT, Sittman DB, Brown DT (December 1999). "Effects of H1 histone variant overexpression on chromatin structure". J. Biol. Chem. 274 (53): 37950–6. doi:10.1074/jbc.274.53.37950. PMID 10608862. 
  15. ^ Maresca TJ, Freedman BS, Heald R (June 2005). "Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts". J. Cell Biol. 169 (6): 859–69. doi:10.1083/jcb.200503031. PMC 2171634. PMID 15967810. 
  16. ^ a b c d Freedman BS, Heald R (June 2010). "Functional Comparison of Linker Histones in Xenopus Reveals Isoform-Specific Regulation by Cdk1 and RanGTP". Curr. Biol. 20 (11): 1048–52. doi:10.1016/j.cub.2010.04.025. PMC 2902237. PMID 20471264. 
  17. ^ Shen X, Yu L, Weir JW, Gorovsky MA (July 1995). "Linker histones are not essential and affect chromatin condensation in vivo". Cell 82 (1): 47–56. doi:10.1016/0092-8674(95)90051-9. PMID 7606784. 
  18. ^ Jedrusik MA, Schulze E (April 2001). "A single histone H1 isoform (H1.1) is essential for chromatin silencing and germline development in Caenorhabditis elegans". Development 128 (7): 1069–80. PMID 11245572. 
  19. ^ Lu X, Wontakal SN, Emelyanov AV, Morcillo P, Konev AY, Fyodorov DV, Skoultchi AI (February 2009). "Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure". Genes Dev. 23 (4): 452–65. doi:10.1101/gad.1749309. PMC 2648648. PMID 19196654. 
  20. ^ Misteli T, Gunjan A, Hock R, Bustin M, Brown DT (December 2000). "Dynamic binding of histone H1 to chromatin in living cells". Nature 408 (6814): 877–81. doi:10.1038/35048610. PMID 11130729. 
  21. ^ Chen D, Dundr M, Wang C, Leung A, Lamond A, Misteli T, Huang S (January 2005). "Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins". J. Cell Biol. 168 (1): 41–54. doi:10.1083/jcb.200407182. PMC 2171683. PMID 15623580. 
  22. ^ Bustin M, Catez F, Lim JH (March 2005). "The dynamics of histone H1 function in chromatin". Mol. Cell 17 (5): 617–20. doi:10.1016/j.molcel.2005.02.019. PMID 15749012. 
  23. ^ Xiao, B.; Freedman, B. S.; Miller, K. E.; Heald, R.; Marko, J. F. (2012). "Histone H1 compacts DNA under force and during chromatin assembly". Molecular Biology of the Cell 23 (24): 4864–4871. doi:10.1091/mbc.E12-07-0518. PMC 3521692. PMID 23097493.  edit
  24. ^ Freedman BS, Miller KE, Heald R (2010). "Xenopus Egg Extracts Increase Dynamics of Histone H1 on Sperm Chromatin". In Cimini, Daniela. PLoS ONE 5 (9): e13111. doi:10.1371/journal.pone.0013111. PMC 2947519. PMID 20927327. 
  25. ^ Steinbach OC, Wolffe AP, Rupp RA (September 1997). "Somatic linker histones cause loss of mesodermal competence in Xenopus". Nature 389 (6649): 395–9. doi:10.1038/38755. PMID 9311783. 
  26. ^ De S, Brown DT, Lu ZH, Leno GH, Wellman SE, Sittman DB (June 2002). "Histone H1 variants differentially inhibit DNA replication through an affinity for chromatin mediated by their carboxyl-terminal domains". Gene 292 (1–2): 173–81. doi:10.1016/S0378-1119(02)00675-3. PMID 12119111. 
  27. ^ a b Izzo A, Kamieniarz K, Schneider R (April 2008). "The histone H1 family: specific members, specific functions?". Biol. Chem. 389 (4): 333–43. doi:10.1515/BC.2008.037. PMID 18208346. 
  28. ^ Khochbin S (June 2001). "Histone H1 diversity: bridging regulatory signals to linker histone function". Gene 271 (1): 1–12. doi:10.1016/S0378-1119(01)00495-4. PMID 11410360. 
  29. ^ Godde JS, Ura K (March 2008). "Cracking the enigmatic linker histone code". J. Biochem. 143 (3): 287–93. doi:10.1093/jb/mvn013. PMID 18234717. 
  30. ^ Happel N, Doenecke D (February 2009). "Histone H1 and its isoforms: contribution to chromatin structure and function". Gene 431 (1–2): 1–12. doi:10.1016/j.gene.2008.11.003. PMID 19059319. 

This page is based on a Wikipedia article. The text is available under the Creative Commons Attribution/Share-Alike License.

This tab holds the annotation information that is stored in the Pfam database. As we move to using Wikipedia as our main source of annotation, the contents of this tab will be gradually replaced by the Wikipedia tab.

linker histone H1 and H5 family Provide feedback

Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures Histone H1 is replaced by histone H5 in some cell types.

Literature references

  1. Ramakrishnan V, Finch JT, Graziano V, Lee PL, Sweet RM; , Nature 1993;362:219-223.: Crystal structure of globular domain of histone H5 and its implications for nucleosome binding. PUBMED:8384699 EPMC:8384699


External database links

This tab holds annotation information from the InterPro database.

InterPro entry IPR005818

Histone proteins have central roles in both chromatin organisation (as structural units of the nucleosome) and gene regulation (as dynamic components that have a direct impact on DNA transcription and replication). Eukaryotic DNA wraps around a histone octamer to form a nucleosome, the first order of compaction of eukaryotic chromatin. The core histone octamer is composed of a central H3-H4 tetramer and two flanking H2A-H2B dimers. Each of the core histone contains a common structural motif, called the histone fold, which facilitates the interactions between the individual core histones.

In addition to the core histones, there is a "linker histone" called H1 (or H5 in avian species). The linker histones present in all multicellular eukaryotes are the most divergent group of histones, with numerous cell type- and stage-specific variant. Linker histone H1 is an essential component of chromatin structure. H1 links nucleosomes into higher order structures. Histone H5 performs the same function as histone H1, and replaces H1 in certain cells. The structure of GH5, the globular domain of the linker histone H5 is known [PUBMED:8384699, PUBMED:3463990]. The fold is similar to the DNA-binding domain of the catabolite gene activator protein, CAP, thus providing a possible model for the binding of GH5 to DNA.

The linker histones, which do not contain the histone fold motif, are critical to the higher-order compaction of chromatin, because they bind to internucleosomal DNA and facilitate interactions between individual nucleosomes. In addition, H1 variants have been shown to be involved in the regulation of developmental genes. A common feature of this protein family is a tripartite structure in which a globular (H15) domain of about 80 amino acids is flanked by two less structured N- and C-terminal tails. The H15 domain is also characterised by high sequence homology among the family of linker histones. The highly conserved H15 domain is essential for the binding of H1 or H5 to the nucleosome. It consists of a three helix bundle (I-III), with a beta-hairpin at the C terminus. There is also a short three-residue stretch between helices I and II that is in the beta-strand conformation. Together with the C-terminal beta-hairpin, this strand forms the third strand of an antiparallel beta-sheet [PUBMED:16345076, PUBMED:8384699, PUBMED:8218199, PUBMED:14654695].

Proteins known to contain a H15 domain are:

  • - Eukaryotic histone H1. The histones H1 constitute a family with many variants, differing in their affinity for chromatin. Several variants are simultaneously present in a single cell. For example, the nucleated erythrocytes of birds contain both H1 and H5, the latter being an extreme variant of H1.
  • - Eukaryotic MHYST family of histone acetyltransferase. Histone acetyltransferases transfer an acetyl group from acetyl-CoA to the epsylon- amino group of lysine within the basic NH2-termini of histones, which bind the acidic phosphates of DNA [PUBMED:15313893].

This entry represents the H15 domain.

Gene Ontology

The mapping between Pfam and Gene Ontology is provided by InterPro. If you use this data please cite InterPro.

Domain organisation

Below is a listing of the unique domain organisations or architectures in which this domain is found. More...

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Alignments

We store a range of different sequence alignments for families. As well as the seed alignment from which the family is built, we provide the full alignment, generated by searching the sequence database using the family HMM. We also generate alignments using four representative proteomes (RP) sets, the NCBI sequence database, and our metagenomics sequence database. More...

View options

We make a range of alignments for each Pfam-A family. You can see a description of each above. You can view these alignments in various ways but please note that some types of alignment are never generated while others may not be available for all families, most commonly because the alignments are too large to handle.

  Seed
(20)
Full
(1947)
Representative proteomes NCBI
(1945)
Meta
(10)
RP15
(258)
RP35
(429)
RP55
(691)
RP75
(991)
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PP/heatmap 1 View  View  View  View  View     
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1Cannot generate PP/Heatmap alignments for seeds; no PP data available

Key: ✓ available, x not generated, not available.

Format an alignment

  Seed
(20)
Full
(1947)
Representative proteomes NCBI
(1945)
Meta
(10)
RP15
(258)
RP35
(429)
RP55
(691)
RP75
(991)
Alignment:
Format:
Order:
Sequence:
Gaps:
Download/view:

Download options

We make all of our alignments available in Stockholm format. You can download them here as raw, plain text files or as gzip-compressed files.

  Seed
(20)
Full
(1947)
Representative proteomes NCBI
(1945)
Meta
(10)
RP15
(258)
RP35
(429)
RP55
(691)
RP75
(991)
Raw Stockholm Download   Download   Download   Download   Download   Download   Download   Download  
Gzipped Download   Download   Download   Download   Download   Download   Download   Download  

You can also download a FASTA format file containing the full-length sequences for all sequences in the full alignment.

External links

MyHits provides a collection of tools to handle multiple sequence alignments. For example, one can refine a seed alignment (sequence addition or removal, re-alignment or manual edition) and then search databases for remote homologs using HMMER3.

Pfam alignments:

HMM logo

HMM logos is one way of visualising profile HMMs. Logos provide a quick overview of the properties of an HMM in a graphical form. You can see a more detailed description of HMM logos and find out how you can interpret them here. More...

Trees

This page displays the phylogenetic tree for this family's seed alignment. We use FastTree to calculate neighbour join trees with a local bootstrap based on 100 resamples (shown next to the tree nodes). FastTree calculates approximately-maximum-likelihood phylogenetic trees from our seed alignment.

Note: You can also download the data file for the tree.

Curation and family details

This section shows the detailed information about the Pfam family. You can see the definitions of many of the terms in this section in the glossary and a fuller explanation of the scoring system that we use in the scores section of the help pages.

Curation View help on the curation process

Seed source: Arne Eloffson
Previous IDs: linker_histone;
Type: Domain
Author: Bateman A
Number in seed: 20
Number in full: 1947
Average length of the domain: 71.20 aa
Average identity of full alignment: 32 %
Average coverage of the sequence by the domain: 23.85 %

HMM information View help on HMM parameters

HMM build commands:
build method: hmmbuild -o /dev/null HMM SEED
search method: hmmsearch -Z 23193494 -E 1000 --cpu 4 HMM pfamseq
Model details:
Parameter Sequence Domain
Gathering cut-off 21.5 21.5
Trusted cut-off 21.5 21.5
Noise cut-off 21.4 21.4
Model length: 77
Family (HMM) version: 14
Download: download the raw HMM for this family

Species distribution

Sunburst controls

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This visualisation provides a simple graphical representation of the distribution of this family across species. You can find the original interactive tree in the adjacent tab. More...

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Tree controls

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The tree shows the occurrence of this domain across different species. More...

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Interactions

There is 1 interaction for this family. More...

Linker_histone

Structures

For those sequences which have a structure in the Protein DataBank, we use the mapping between UniProt, PDB and Pfam coordinate systems from the PDBe group, to allow us to map Pfam domains onto UniProt sequences and three-dimensional protein structures. The table below shows the structures on which the Linker_histone domain has been found. There are 9 instances of this domain found in the PDB. Note that there may be multiple copies of the domain in a single PDB structure, since many structures contain multiple copies of the same protein seqence.

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