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词条 Histone H1
释义

  1. Structure

  2. Function

  3. Dynamics

  4. Isoforms

  5. Post-translational Modifications

  6. See also

  7. References

{{Pfam_box
| Symbol = Linker_histone
| Name = linker histone H1 and H5 family
| image = PBB_Protein_HIST1H1B_image.jpg
| width =
| caption = PDB rendering of HIST1H1B based on 1ghc.
| Pfam = PF00538
| Pfam_clan =
| InterPro = IPR005818
| SMART = SM00526
| PROSITE =
| SCOP = 1hst
| TCDB =
| OPM family =
| OPM protein =
| PDB = {{PDB2|1ghc}}, {{PDB2|1hst}}, {{PDB2|1uhm}}, {{PDB2|1uss}}, {{PDB2|1ust}}, {{PDB2|1yqa}}
}}

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

Metazoan H1 proteins feature a central globular "winged helix" 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] H1 found in protists and bacteria, otherwise known as nucleoprotein HC1/HC2, lack the central domain and the N-terminal tail.[2]

H1 is less conserved than core histones. The globular domain is the most conserved part of H1.[3]

Function

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.[3] 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.[4][5][6]

It is uncertain whether H1 promotes a solenoid-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[7] However, linker histones have been demonstrated to drive the compaction of chromatin fibres that had been reconstituted in vitro using synthetic DNA arrays of the strong '601' nucleosome positioning element. [8] 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.[9][10][11][12] In addition, experiments on reconstituted chromatin reveal a characteristic stem motif at the dyad in the presence of H1.[13] 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.[7][11]

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.[14][15][16] 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.[17][18] 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.[19][20][21]

Dynamics

While most histone H1 in the nucleus is bound to chromatin, H1 molecules shuttle between chromatin regions at a fairly high rate.[22][23]

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.[24] 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.[25]

Cytoplasmic factors appear to be necessary for the dynamic exchange of histone H1 on chromatin, but these have yet to be specifically identified.[26] 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.[18]

Isoforms

{{main|Linker histone H1 variants}}

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.[27][28][29] One isoform is histone H5, which is only found in avian erythrocytes, which are unlike mammalian erythrocytes in that they 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.[29][30][31][32] Despite having more negative charges than somatic isoforms, H1M binds with higher affinity to mitotic chromosomes in Xenopus egg extracts.[18]

Post-translational Modifications

Like other histones, the histone H1 family is extensively post-translationally modified (PTMs). This includes serine and threonine phosphorylation, lysine acetylation, lysine methylation and ubiquitination. [33] These PTMs serve a variety of functions but are less well studied than the PTMs of other histones.

See also

  • nucleosome
  • histone
  • chromatin
  • linker histone H1 variants
  • Other histone proteins involved in chromatin:
  • H2A
  • H2B
  • H3
  • H4

References

1. ^{{cite journal |vauthors=Ramakrishnan V, Finch JT, Graziano V, Lee PL, Sweet RM | title = Crystal structure of globular domain of histone H5 and its implications for nucleosome binding | journal = Nature | volume = 362 | issue = 6417 | pages = 219–23 |date=March 1993 | pmid = 8384699 | doi = 10.1038/362219a0 | url = }}
2. ^{{cite journal |last1=KASINSKY |first1=HAROLD E. |last2=LEWIS |first2=JOHN D. |last3=DACKS |first3=JOEL B. |last4=AUSIÓ |first4=JUAN |title=Origin of H1 linker histones |journal=The FASEB Journal |date=January 2001 |volume=15 |issue=1 |pages=34–42 |doi=10.1096/fj.00-0237rev |pmid=11149891}}
3. ^{{cite book |author1=Jeon, Kwang W. |author2=Berezney, Ronald | title = Structural and functional organization of the nuclear matrix | edition = | language = | publisher = Academic Press | location = Boston | year = 1995 | origyear = | pages = 214–7 | quote = | isbn = 978-0-12-364565-4 | oclc = | doi = | url = | accessdate = }}
4. ^{{cite journal |vauthors=Finch JT, Klug A | title = Solenoidal model for superstructure in chromatin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 73 | issue = 6 | pages = 1897–901 |date=June 1976 | pmid = 1064861 | pmc = 430414 | doi = 10.1073/pnas.73.6.1897| url = }}
5. ^{{cite journal |vauthors=Thoma F, Koller T | title = Influence of histone H1 on chromatin structure | journal = Cell | volume = 12 | issue = 1 | pages = 101–7 |date=September 1977 | pmid = 561660 | doi = 10.1016/0092-8674(77)90188-X| url = }}
6. ^{{cite journal |vauthors=Thoma F, Koller T, Klug A | title = Involvement of histone H1 in the organization of the nucleosome and of the salt-dependent superstructures of chromatin | journal = J. Cell Biol. | volume = 83 | issue = 2 Pt 1 | pages = 403–27 |date=November 1979 | pmid = 387806 | pmc = 2111545 | doi = 10.1083/jcb.83.2.403| url = }}
7. ^1 {{cite journal |vauthors=van Holde K, Zlatanova J | title = What determines the folding of the chromatin fiber? | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 20 | pages = 10548–55 |date=October 1996 | pmid = 8855215 | pmc = 38190 | doi = 10.1073/pnas.93.20.10548| url = }}
8. ^{{cite journal|last1=Routh|first1=A|last2=Sandin|first2=S|last3=Rhodes|first3=D|title=Nucleosome repeat length and linker histone stoichiometry determine chromatin fiber structure.|journal=Proceedings of the National Academy of Sciences of the United States of America|date=1 July 2008|volume=105|issue=26|pages=8872–7|doi=10.1073/pnas.0802336105|pmid=18583476|pmc=2440727}}
9. ^{{cite journal |vauthors=Varshavsky AJ, Bakayev VV, Georgiev GP | title = Heterogeneity of chromatin subunits in vitro and location of histone H1 | journal = Nucleic Acids Res. | volume = 3 | issue = 2 | pages = 477–92 |date=February 1976 | pmid = 1257057 | pmc = 342917 | doi = 10.1093/nar/3.2.477| url = }}
10. ^{{cite journal |vauthors=Whitlock JP, Simpson RT | title = Removal of histone H1 exposes a fifty base pair DNA segment between nucleosomes | journal = Biochemistry | volume = 15 | issue = 15 | pages = 3307–14 |date=July 1976 | pmid = 952859 | doi = 10.1021/bi00660a022| url = }}
11. ^1 {{cite journal |vauthors=Allan J, Hartman PG, Crane-Robinson C, Aviles FX | title = The structure of histone H1 and its location in chromatin | journal = Nature | volume = 288 | issue = 5792 | pages = 675–9 |date=December 1980 | pmid = 7453800 | doi = 10.1038/288675a0| url = }}
12. ^{{cite journal |vauthors=Staynov DZ, Crane-Robinson C | title = Footprinting of linker histones H5 and H1 on the nucleosome | journal = EMBO J. | volume = 7 | issue = 12 | pages = 3685–91 |date=December 1988 | pmid = 3208745 | pmc = 454941 | doi = 10.1002/j.1460-2075.1988.tb03250.x| url = }}
13. ^{{cite journal |vauthors=Bednar J, Horowitz RA, Grigoryev SA, Carruthers LM, Hansen JC, Koster AJ, Woodcock CL | title = Nucleosomes, linker DNA, and linker histone form a unique structural motif that directs the higher-order folding and compaction of chromatin | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 95 | issue = 24 | pages = 14173–8 |date=November 1998 | pmid = 9826673 | pmc = 24346 | doi = 10.1073/pnas.95.24.14173| url = }}
14. ^{{cite journal |vauthors=Dworkin-Rastl E, Kandolf H, Smith RC | title = The maternal histone H1 variant, H1M (B4 protein), is the predominant H1 histone in Xenopus pregastrula embryos | journal = Dev. Biol. | volume = 161 | issue = 2 | pages = 425–39 |date=February 1994 | pmid = 8313993 | doi = 10.1006/dbio.1994.1042 | url = }}
15. ^{{cite journal |vauthors=Brown DT, Alexander BT, Sittman DB | title = Differential effect of H1 variant overexpression on cell cycle progression and gene expression | journal = Nucleic Acids Res. | volume = 24 | issue = 3 | pages = 486–93 |date=February 1996 | pmid = 8602362 | pmc = 145659 | doi = 10.1093/nar/24.3.486| url = }}
16. ^{{cite journal |vauthors=Gunjan A, Alexander BT, Sittman DB, Brown DT | title = Effects of H1 histone variant overexpression on chromatin structure | journal = J. Biol. Chem. | volume = 274 | issue = 53 | pages = 37950–6 |date=December 1999 | pmid = 10608862 | doi = 10.1074/jbc.274.53.37950| url = }}
17. ^{{cite journal |vauthors=Maresca TJ, Freedman BS, Heald R | title = Histone H1 is essential for mitotic chromosome architecture and segregation in Xenopus laevis egg extracts | journal = J. Cell Biol. | volume = 169 | issue = 6 | pages = 859–69 |date=June 2005 | pmid = 15967810 | pmc = 2171634 | doi = 10.1083/jcb.200503031 | url = }}
18. ^1 2 {{cite journal |vauthors=Freedman BS, Heald R | title = Functional Comparison of Linker Histones in Xenopus Reveals Isoform-Specific Regulation by Cdk1 and RanGTP | journal = Curr. Biol. | volume = 20 | issue = 11 | pages = 1048–52 |date=June 2010 | pmid = 20471264 | pmc = 2902237 | doi = 10.1016/j.cub.2010.04.025 | url = }}
19. ^{{cite journal |vauthors=Shen X, Yu L, Weir JW, Gorovsky MA | title = Linker histones are not essential and affect chromatin condensation in vivo | journal = Cell | volume = 82 | issue = 1 | pages = 47–56 |date=July 1995 | pmid = 7606784 | doi = 10.1016/0092-8674(95)90051-9| url = }}
20. ^{{cite journal |vauthors=Jedrusik MA, Schulze E | title = A single histone H1 isoform (H1.1) is essential for chromatin silencing and germline development in Caenorhabditis elegans | journal = Development | volume = 128 | issue = 7 | pages = 1069–80 |date=April 2001 | pmid = 11245572 | doi = | url = }}
21. ^{{cite journal |vauthors=Lu X, Wontakal SN, Emelyanov AV, Morcillo P, Konev AY, Fyodorov DV, Skoultchi AI | title = Linker histone H1 is essential for Drosophila development, the establishment of pericentric heterochromatin, and a normal polytene chromosome structure | journal = Genes Dev. | volume = 23 | issue = 4 | pages = 452–65 |date=February 2009 | pmid = 19196654 | pmc = 2648648 | doi = 10.1101/gad.1749309 | url = }}
22. ^{{cite journal |vauthors=Misteli T, Gunjan A, Hock R, Bustin M, Brown DT | title = Dynamic binding of histone H1 to chromatin in living cells | journal = Nature | volume = 408 | issue = 6814 | pages = 877–81 |date=December 2000 | pmid = 11130729 | doi = 10.1038/35048610 | url = }}
23. ^{{cite journal |vauthors=Chen D, Dundr M, Wang C, Leung A, Lamond A, Misteli T, Huang S | title = Condensed mitotic chromatin is accessible to transcription factors and chromatin structural proteins | journal = J. Cell Biol. | volume = 168 | issue = 1 | pages = 41–54 |date=January 2005 | pmid = 15623580 | pmc = 2171683 | doi = 10.1083/jcb.200407182 | url = }}
24. ^{{cite journal |vauthors=Bustin M, Catez F, Lim JH | title = The dynamics of histone H1 function in chromatin | journal = Mol. Cell | volume = 17 | issue = 5 | pages = 617–20 |date=March 2005 | pmid = 15749012 | doi = 10.1016/j.molcel.2005.02.019 | url = }}
25. ^{{Cite journal | last1 = Xiao | first1 = B. | last2 = Freedman | first2 = B. S. | last3 = Miller | first3 = K. E. | last4 = Heald | first4 = R. | last5 = Marko | first5 = J. F. | title = Histone H1 compacts DNA under force and during chromatin assembly | doi = 10.1091/mbc.E12-07-0518 | journal = Molecular Biology of the Cell | volume = 23 | issue = 24 | pages = 4864–4871 | year = 2012 | pmid = 23097493 | pmc =3521692 }}
26. ^{{cite journal | vauthors = Freedman BS, Miller KE, Heald R | title = Xenopus Egg Extracts Increase Dynamics of Histone H1 on Sperm Chromatin | journal = PLoS ONE | volume = 5 | issue = 9 | pages = e13111| year = 2010 | pmid = 20927327 | pmc = 2947519 | doi = 10.1371/journal.pone.0013111 | url = | editor1-last = Cimini | editor1-first = Daniela }}
27. ^{{cite journal |vauthors=Steinbach OC, Wolffe AP, Rupp RA | title = Somatic linker histones cause loss of mesodermal competence in Xenopus | journal = Nature | volume = 389 | issue = 6649 | pages = 395–9 |date=September 1997 | pmid = 9311783 | doi = 10.1038/38755 | url = }}
28. ^{{cite journal |vauthors=De S, Brown DT, Lu ZH, Leno GH, Wellman SE, Sittman DB | title = Histone H1 variants differentially inhibit DNA replication through an affinity for chromatin mediated by their carboxyl-terminal domains | journal = Gene | volume = 292 | issue = 1–2 | pages = 173–81 |date=June 2002 | pmid = 12119111 | doi = 10.1016/S0378-1119(02)00675-3| url = }}
29. ^1 2 {{cite journal |vauthors=Izzo A, Kamieniarz K, Schneider R | title = The histone H1 family: specific members, specific functions? | journal = Biol. Chem. | volume = 389 | issue = 4 | pages = 333–43 |date=April 2008 | pmid = 18208346 | doi = 10.1515/BC.2008.037 | url = }}
30. ^{{cite journal | author = Khochbin S | title = Histone H1 diversity: bridging regulatory signals to linker histone function | journal = Gene | volume = 271 | issue = 1 | pages = 1–12 |date=June 2001 | pmid = 11410360 | doi = 10.1016/S0378-1119(01)00495-4| url = }}
31. ^{{cite journal |vauthors=Godde JS, Ura K | title = Cracking the enigmatic linker histone code | journal = J. Biochem. | volume = 143 | issue = 3 | pages = 287–93 |date=March 2008 | pmid = 18234717 | doi = 10.1093/jb/mvn013 | url = }}
32. ^{{cite journal |vauthors=Happel N, Doenecke D | title = Histone H1 and its isoforms: contribution to chromatin structure and function | journal = Gene | volume = 431 | issue = 1–2 | pages = 1–12 |date=February 2009 | pmid = 19059319 | doi = 10.1016/j.gene.2008.11.003 | url = }}
33. ^{{cite journal |vauthors=Harshman SW, Young NL, Parthun MR, Freitas MA | title = H1 histones: current perspectives and challenges | journal = Nucleic Acids Res. | volume = 21 | issue = 41 | pages = 9593–609 |date=August 2013 | pmid = 23945933 | pmc = 3834806 | doi = 10.1093/nar/gkt700 | url = }}
{{Chromo}}{{Use dmy dates|date=January 2012}}

1 : Proteins
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