Linker histone H1 variants

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Diagram showing the linker histone H1 binding to the nucleosome H1 binding to the nucleosome.png
Diagram showing the linker histone H1 binding to the nucleosome

In molecular biology, the linker histone H1 is a protein family forming a critical component of eukaryotic chromatin. H1 histones bind to the linker DNA exiting from the nucleosome core particle, while the core histones (H2A, H2B, H3 and H4) form the octamer core of the nucleosome around which the DNA is wrapped. [1]

Contents

H1 forms a complex family of related proteins with distinct specificity for tissues, developmental stages, and organisms in which they are expressed. [2] Individual H1 proteins are often referred to as isoforms or variants.

The discovery of H1 variants in calf thymus preceded the discovery of core histone variants. [3] [4]

Evolutionary tree of eukaryotes showing in brackets the number of known linker histone H1 variants in a given species (see original data in ) Linker histone variant evolutionary tree.png
Evolutionary tree of eukaryotes showing in brackets the number of known linker histone H1 variants in a given species (see original data in )

Human linker histone variants

In human and mouse cells 11 H1 variants have been described and are encoded by single genes. Six of the variants are mainly expressed during the S phase and hence replication-dependent. They are encoded by genes within histone cluster 1 located in human cells on chromosome 6. The five further variants are expressed over the whole cell cycle and their encoding genes are scattered in the genome.

Human gene symbolUnified phylogeny-based nomenclature [5]
H1 variants within histone gene cluster 1 (replication dependent)
HIST1H1AH1.1
HIST1H1BH1.5
HIST1H1CH1.2
HIST1H1DH1.3
HIST1H1EH1.4
HIST1H1T(TS) H1.6
H1 variants encoded by orphan genes (replication independent)
H1F0H1.0
H1FNT(TS) H1.7
H1FOO(OO) H1.8
HILS1(TS) H1.9
H1FXH1.10

TS - testis specific, OO - oocyte specific variants

Evolution

Histone H1 differs strongly from the core histones. Rather than originating from archaeal histones, it probably evolved from a bacterial protein. [6] Unlike core histones featuring a so-called histone fold, H1s typically have a short basic N-terminal domain, a globular domain and a lysine-rich C-terminal domain (the N- and C-termini are also referred to as tails). [7] H1s are also less conserved than the core histones. The mammalian H1 isoforms are paralogs, which means their encoding genes originated from gene duplication events. The corresponding H1 variants in two different species, such as human and mouse H1.4 are orthologs – they had a common ancestor gene and were separated by speciation. Within one species, the paralogous H1 variants show a high conservation of the globular core domain, while the N- and C-termini are more divergent. At the same time H1 orthologs among mammals are highly conserved across the whole protein sequence, for example human and mouse H1.4 share 93.6% sequence identity. [2]

Function

The extent to which individual H1 variants can be redundant and what their distinct functions are isn't yet clear. The fact that many individual H1 variant knockouts in mice are viable and show compensation by other H1 variants seems to support the hypothesis of redundancy. [8] [9] [10] [11] However, many lines of evidence suggest specific functions exist for H1 variants. For example, individual H1 variant knockout mice reveal specific phenotypes and distinct effects on gene expression and chromatin structure. [9] [10] [12] [13] [14] [15] Also, different isotypes show different localization and bind to chromatin with different affinities. [16] [17] [18] [19] [20] [21]

Therefore, a model has been proposed according to which H1 variants have two distinct roles, a common and a specific one: [2] Individual H1 proteins are redundant in their ability to compact chromatin globally and to stabilize overall higher order chromatin structures. Such a common role can therefore be compensated in mutant cells by increasing the amount of other H1 variants. However, at the level of local chromatin organization, individual variants can regulate a subset of specific genes both in a negative and positive way. [2]

Nomenclature

Multiple nomenclatures (around 12) for linker histone variants have been proposed and used in publications previously, greatly complicating comparison across studies. In 1994 Parseghian et al. have attempted to create a system in which variant designations were applied uniformly to orthologs across mammalian species, [22] however this nomenclature hasn't been taken up by other laboratories. In 2012, a diverse group of scientists from multiple institutions across the world working on different aspects of histone biology proposed a unified phylogeny-based nomenclature for histone variants, including H1 histones, with the aim of producing informative and easily searchable histone variant names. [5]

See also

Related Research Articles

Chromatin is a complex of DNA and protein found in eukaryotic cells. The primary function is to package long DNA molecules into more compact, denser structures. This prevents the strands from becoming tangled and also plays important roles in reinforcing the DNA during cell division, preventing DNA damage, and regulating gene expression and DNA replication. During mitosis and meiosis, chromatin facilitates proper segregation of the chromosomes in anaphase; the characteristic shapes of chromosomes visible during this stage are the result of DNA being coiled into highly condensed chromatin.

<span class="mw-page-title-main">Histone</span> Protein family around which DNA winds to form nucleosomes

In biology, histones are highly basic proteins abundant in lysine and arginine residues that are found in eukaryotic cell nuclei and in most Archaeal phyla. They act as spools around which DNA winds to create structural units called nucleosomes. Nucleosomes in turn are wrapped into 30-nanometer fibers that form tightly packed chromatin. Histones prevent DNA from becoming tangled and protect it from DNA damage. In addition, histones play important roles in gene regulation and DNA replication. Without histones, unwound DNA in chromosomes would be very long. For example, each human cell has about 1.8 meters of DNA if completely stretched out; however, when wound about histones, this length is reduced to about 90 micrometers (0.09 mm) of 30 nm diameter chromatin fibers.

<span class="mw-page-title-main">Nucleosome</span> Basic structural unit of DNA packaging in eukaryotes

A nucleosome is the basic structural unit of DNA packaging in eukaryotes. The structure of a nucleosome consists of a segment of DNA wound around eight histone proteins and resembles thread wrapped around a spool. The nucleosome is the fundamental subunit of chromatin. Each nucleosome is composed of a little less than two turns of DNA wrapped around a set of eight proteins called histones, which are known as a histone octamer. Each histone octamer is composed of two copies each of the histone proteins H2A, H2B, H3, and H4.

HMGN proteins are members of the broader class of high mobility group (HMG) chromosomal proteins that are involved in regulation of transcription, replication, recombination, and DNA repair.

<span class="mw-page-title-main">Histone H1</span> Components of chromatin in eukaryotic cells

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.

<span class="mw-page-title-main">Histone H3</span> One of the five main histone proteins

Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H3 is involved with the structure of the nucleosomes of the 'beads on a string' structure. Histone proteins are highly post-translationally modified however Histone H3 is the most extensively modified of the five histones. The term "Histone H3" alone is purposely ambiguous in that it does not distinguish between sequence variants or modification state. Histone H3 is an important protein in the emerging field of epigenetics, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes.

<span class="mw-page-title-main">Histone H4</span> One of the five main histone proteins involved in the structure of chromatin

Histone H4 is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells. Featuring a main globular domain and a long N-terminal tail, H4 is involved with the structure of the nucleosome of the 'beads on a string' organization. Histone proteins are highly post-translationally modified. Covalently bonded modifications include acetylation and methylation of the N-terminal tails. These modifications may alter expression of genes located on DNA associated with its parent histone octamer. Histone H4 is an important protein in the structure and function of chromatin, where its sequence variants and variable modification states are thought to play a role in the dynamic and long term regulation of genes.

<span class="mw-page-title-main">Histone H2A</span> One of the five main histone proteins

Histone H2A is one of the five main histone proteins involved in the structure of chromatin in eukaryotic cells.

<span class="mw-page-title-main">Solenoid (DNA)</span>

The solenoid structure of chromatin is a model for the structure of the 30 nm fibre. It is a secondary chromatin structure which helps to package eukaryotic DNA into the nucleus.

Chromatin remodeling is the dynamic modification of chromatin architecture to allow access of condensed genomic DNA to the regulatory transcription machinery proteins, and thereby control gene expression. Such remodeling is principally carried out by 1) covalent histone modifications by specific enzymes, e.g., histone acetyltransferases (HATs), deacetylases, methyltransferases, and kinases, and 2) ATP-dependent chromatin remodeling complexes which either move, eject or restructure nucleosomes. Besides actively regulating gene expression, dynamic remodeling of chromatin imparts an epigenetic regulatory role in several key biological processes, egg cells DNA replication and repair; apoptosis; chromosome segregation as well as development and pluripotency. Aberrations in chromatin remodeling proteins are found to be associated with human diseases, including cancer. Targeting chromatin remodeling pathways is currently evolving as a major therapeutic strategy in the treatment of several cancers.

<span class="mw-page-title-main">Histone H2A.Z</span> Protein-coding gene in the species Homo sapiens

Histone H2A.Z is a protein that in humans is encoded by the H2AZ1 gene.

Histones are basic nuclear proteins that are responsible for the nucleosome structure of the chromosomal fiber in eukaryotes. Nucleosomes consist of approximately 146 bp of DNA wrapped around a histone octamer composed of pairs of each of the four core histones. The chromatin fiber is further compacted through the interaction of a linker histone, H1, with the DNA between the nucleosomes to form higher order chromatin structures. The H2AFZ gene encodes a replication-independent member of the histone H2A family that is distinct from other members of the family. Studies in mice have shown that this particular histone is required for embryonic development and indicate that lack of functional histone H2A leads to embryonic lethality.

<span class="mw-page-title-main">HIST1H4I</span> Protein-coding gene in the species Homo sapiens

Histone H4 is a protein that, in humans, is encoded by the HIST1H4I gene.

<span class="mw-page-title-main">HIST1H1B</span> Protein-coding gene in the species Homo sapiens

Histone H1.5 is a protein that in humans is encoded by the HIST1H1B gene.

<span class="mw-page-title-main">HIST1H2BD</span> Protein-coding gene in the species Homo sapiens

Histone H2B type 1-D is a protein that in humans is encoded by the HIST1H2BD gene.

<span class="mw-page-title-main">HIST1H1A</span> Protein-coding gene in the species Homo sapiens

Histone H1.1 is a protein that in humans is encoded by the HIST1H1A gene.

<span class="mw-page-title-main">HIST1H1E</span> Protein-coding gene in the species Homo sapiens

Histone H1.4 is a protein that in humans is encoded by the HIST1H1E gene.

<span class="mw-page-title-main">HIST1H1C</span> Protein-coding gene in the species Homo sapiens

Histone H1.2 is a protein that in humans is encoded by the HIST1H1C gene.

<span class="mw-page-title-main">CHD8</span> Protein-coding gene in the species Homo sapiens

Chromodomain-helicase-DNA-binding protein 8 is an enzyme that in humans is encoded by the CHD8 gene.

<span class="mw-page-title-main">H1FX</span> Protein-coding gene in the species Homo sapiens

Histone H1x is a protein that in humans is encoded by the H1FX gene.

Histone variants are proteins that substitute for the core canonical histones in nucleosomes in eukaryotes and often confer specific structural and functional features. The term might also include a set of linker histone (H1) variants, which lack a distinct canonical isoform. The differences between the core canonical histones and their variants can be summarized as follows: (1) canonical histones are replication-dependent and are expressed during the S-phase of cell cycle whereas histone variants are replication-independent and are expressed during the whole cell cycle; (2) in animals, the genes encoding canonical histones are typically clustered along the chromosome, are present in multiple copies and are among the most conserved proteins known, whereas histone variants are often single-copy genes and show high degree of variation among species; (3) canonical histone genes lack introns and use a stem loop structure at the 3’ end of their mRNA, whereas histone variant genes may have introns and their mRNA tail is usually polyadenylated. Complex multicellular organisms typically have a large number of histone variants providing a variety of different functions. Recent data are accumulating about the roles of diverse histone variants highlighting the functional links between variants and the delicate regulation of organism development.

References

  1. ↑ Jordan, Albert (2016-03-01). "Histone H1 in gene expression and development". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (3): 429–430. doi:10.1016/j.bbagrm.2016.01.001. hdl: 10261/133904 . ISSN   0006-3002. PMID   26772994.
  2. 1 2 3 4 5 Izzo, Annalisa; Kamieniarz, Kinga; Schneider, Robert (2008-04-01). "The histone H1 family: specific members, specific functions?". Biological Chemistry. 389 (4): 333–343. doi:10.1515/BC.2008.037. ISSN   1431-6730. PMID   18208346. S2CID   1516241.
  3. ↑ Kinkade, JM; Cole, RD (Dec 25, 1966). "The resolution of four lysine-rich histones derived from calf thymus". J Biol Chem. 241 (24): 5790–7. doi: 10.1016/S0021-9258(18)96342-8 . PMID   5954358.
  4. ↑ Kinkade, JM; Cole, RD (Dec 25, 1966). "A structural comparison of different lysine-rich histones of calf thymus". J Biol Chem. 241 (24): 5798–805. doi: 10.1016/S0021-9258(18)96343-X . PMID   5954359.
  5. 1 2 Talbert, Paul B.; Ahmad, Kami; Almouzni, Geneviève; Ausió, Juan; Berger, Frederic; Bhalla, Prem L.; Bonner, William M.; Cande, W. Zacheus; Chadwick, Brian P. (2012-01-01). "A unified phylogeny-based nomenclature for histone variants". Epigenetics & Chromatin . 5: 7. doi: 10.1186/1756-8935-5-7 . ISSN   1756-8935. PMC   3380720 . PMID   22650316.
  6. ↑ Kasinsky, H. E.; Lewis, J. D.; Dacks, J. B.; Ausió, J. (2001-01-01). "Origin of H1 linker histones". FASEB Journal. 15 (1): 34–42. doi: 10.1096/fj.00-0237rev . ISSN   0892-6638. PMID   11149891. S2CID   10089116.
  7. ↑ Crane-Robinson, C. (2016-03-01). "Linker histones: History and current perspectives". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (3): 431–435. doi:10.1016/j.bbagrm.2015.10.008. ISSN   0006-3002. PMID   26459501.
  8. ↑ Fan, Y.; Sirotkin, A.; Russell, R. G.; Ayala, J.; Skoultchi, A. I. (2001-12-01). "Individual somatic H1 subtypes are dispensable for mouse development even in mice lacking the H1(0) replacement subtype". Molecular and Cellular Biology. 21 (23): 7933–7943. doi:10.1128/MCB.21.23.7933-7943.2001. ISSN   0270-7306. PMC   99962 . PMID   11689686.
  9. 1 2 Fan, Yuhong; Nikitina, Tatiana; Morin-Kensicki, Elizabeth M.; Zhao, Jie; Magnuson, Terry R.; Woodcock, Christopher L.; Skoultchi, Arthur I. (2003-07-01). "H1 linker histones are essential for mouse development and affect nucleosome spacing in vivo". Molecular and Cellular Biology. 23 (13): 4559–4572. doi:10.1128/mcb.23.13.4559-4572.2003. ISSN   0270-7306. PMC   164858 . PMID   12808097.
  10. 1 2 Alami, Raouf; Fan, Yuhong; Pack, Stephanie; Sonbuchner, Timothy M.; Besse, Arnaud; Lin, Qingcong; Greally, John M.; Skoultchi, Arthur I.; Bouhassira, Eric E. (2003-05-13). "Mammalian linker-histone subtypes differentially affect gene expression in vivo". Proceedings of the National Academy of Sciences of the United States of America. 100 (10): 5920–5925. Bibcode:2003PNAS..100.5920A. doi: 10.1073/pnas.0736105100 . ISSN   0027-8424. PMC   156302 . PMID   12719535.
  11. ↑ Sirotkin, AM; Edelmann, W; Cheng, G; Klein-Szanto, A; Kucherlapati, R; Skoultchi, AI (3 July 1995). "Mice develop normally without the H1(0) linker histone". Proc Natl Acad Sci U S A. 92 (14): 6434–8. Bibcode:1995PNAS...92.6434S. doi: 10.1073/pnas.92.14.6434 . PMC   41532 . PMID   7604008.
  12. ↑ Fan, Yuhong; Nikitina, Tatiana; Zhao, Jie; Fleury, Tomara J.; Bhattacharyya, Riddhi; Bouhassira, Eric E.; Stein, Arnold; Woodcock, Christopher L.; Skoultchi, Arthur I. (2005-12-29). "Histone H1 depletion in mammals alters global chromatin structure but causes specific changes in gene regulation". Cell. 123 (7): 1199–1212. doi: 10.1016/j.cell.2005.10.028 . ISSN   0092-8674. PMID   16377562. S2CID   8378657.
  13. ↑ Gabrilovich, Dmitry I.; Cheng, Pingyan; Fan, Yuhong; Yu, Bin; Nikitina, Ekaterina; Sirotkin, Allen; Shurin, Michael; Oyama, Tsunehiro; Adachi, Yasushi (2002-08-01). "H1(0) histone and differentiation of dendritic cells. A molecular target for tumor-derived factors". Journal of Leukocyte Biology. 72 (2): 285–296. doi: 10.1189/jlb.72.2.285 . ISSN   0741-5400. PMID   12149419. S2CID   40524167.
  14. ↑ Martianov, Igor; Brancorsini, Stefano; Catena, Raffaella; Gansmuller, Anne; Kotaja, Noora; Parvinen, Martti; Sassone-Corsi, Paolo; Davidson, Irwin (2005-02-22). "Polar nuclear localization of H1T2, a histone H1 variant, required for spermatid elongation and DNA condensation during spermiogenesis". Proceedings of the National Academy of Sciences of the United States of America. 102 (8): 2808–2813. Bibcode:2005PNAS..102.2808M. doi: 10.1073/pnas.0406060102 . ISSN   0027-8424. PMC   549447 . PMID   15710904.
  15. ↑ Tanaka, Hiromitsu; Iguchi, Naoko; Isotani, Ayako; Kitamura, Kouichi; Toyama, Yoshiro; Matsuoka, Yasuhiro; Onishi, Masayoshi; Masai, Kumiko; Maekawa, Mamiko (2005-08-01). "HANP1/H1T2, a novel histone H1-like protein involved in nuclear formation and sperm fertility". Molecular and Cellular Biology. 25 (16): 7107–7119. doi:10.1128/MCB.25.16.7107-7119.2005. ISSN   0270-7306. PMC   1190238 . PMID   16055721.
  16. ↑ Parseghian, M. H.; Newcomb, R. L.; Winokur, S. T.; Hamkalo, B. A. (2000-01-01). "The distribution of somatic H1 subtypes is non-random on active vs. inactive chromatin: distribution in human fetal fibroblasts". Chromosome Research. 8 (5): 405–424. doi:10.1023/A:1009262819961. ISSN   0967-3849. PMID   10997781. S2CID   28425496.
  17. ↑ Th'ng, John P. H.; Sung, Rohyun; Ye, Ming; Hendzel, Michael J. (2005-07-29). "H1 family histones in the nucleus. Control of binding and localization by the C-terminal domain". The Journal of Biological Chemistry. 280 (30): 27809–27814. doi: 10.1074/jbc.M501627200 . ISSN   0021-9258. PMID   15911621.
  18. ↑ Orrego, Mary; Ponte, Imma; Roque, Alicia; Buschati, Natascha; Mora, Xavier; Suau, Pedro (2007-01-01). "Differential affinity of mammalian histone H1 somatic subtypes for DNA and chromatin". BMC Biology. 5: 22. doi: 10.1186/1741-7007-5-22 . ISSN   1741-7007. PMC   1890542 . PMID   17498293.
  19. ↑ Izzo, Annalisa; Kamieniarz-Gdula, Kinga; Ramírez, Fidel; Noureen, Nighat; Kind, Jop; Manke, Thomas; van Steensel, Bas; Schneider, Robert (2013-06-27). "The genomic landscape of the somatic linker histone subtypes H1.1 to H1.5 in human cells". Cell Reports. 3 (6): 2142–2154. doi: 10.1016/j.celrep.2013.05.003 . ISSN   2211-1247. PMID   23746450.
  20. ↑ Millán-Ariño, Lluís; Islam, Abul B. M. M. K.; Izquierdo-Bouldstridge, Andrea; Mayor, Regina; Terme, Jean-Michel; Luque, Neus; Sancho, Mónica; López-Bigas, Núria; Jordan, Albert (2014-04-01). "Mapping of six somatic linker histone H1 variants in human breast cancer cells uncovers specific features of H1.2". Nucleic Acids Research. 42 (7): 4474–4493. doi:10.1093/nar/gku079. ISSN   1362-4962. PMC   3985652 . PMID   24476918.
  21. ↑ Millán-Ariño, Lluís; Izquierdo-Bouldstridge, Andrea; Jordan, Albert (2016-03-01). "Specificities and genomic distribution of somatic mammalian histone H1 subtypes". Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms. 1859 (3): 510–519. doi:10.1016/j.bbagrm.2015.10.013. ISSN   0006-3002. PMID   26477490.
  22. ↑ Parseghian, MH; Henschen, AH; Krieglstein, KG; Hamkalo, BA (April 1994). "A proposal for a coherent mammalian histone H1 nomenclature correlated with amino acid sequences". Protein Sci. 3 (4): 575–87. doi:10.1002/pro.5560030406. PMC   2142865 . PMID   8003976.
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