Histone H3 Explained

H3 histone, family 3A (H3.3A)
Hgncid:4764
Symbol:H3F3A
Altsymbols:H3F3
Entrezgene:3020
Omim:601128
Refseq:NM_002107
Uniprot:Q66I33
Chromosome:1
Arm:q
Band:41
H3 histone, family 3B (H3.3B)
Hgncid:4765
Symbol:H3F3B
Entrezgene:3021
Omim:601058
Refseq:NM_005324
Uniprot:P84243
Chromosome:17
Arm:q
Band:25

Histone H3 is one of the five main histones involved in the structure of chromatin in eukaryotic cells.[1] [2] 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.

Epigenetics and post-translational modifications

The N-terminus of H3 protrudes from the globular nucleosome core and is susceptible to post-translational modification that influence cellular processes. These modifications include the covalent attachment of methyl or acetyl groups to lysine and arginine amino acids and the phosphorylation of serine or threonine. Di- and Tri-methylation of lysine 9 are associated with repression and heterochromatin (see H3K9me2 and H3K9me3), while mono-methylation of K4 (K4 corresponds to lysine residue at 4th position)(see H3K4me1), is associated with active genes.[3] [4] Acetylation of histone H3 at several lysine positions in the histone tail is performed by histone acetyltransferase enzymes (HATs). Acetylation of lysine14 is commonly seen in genes that are being actively transcribed into RNA (see H3K14ac).

Sequence variants

Mammalian cells have seven known sequence variants of histone H3. These are denoted as Histone H3.1, Histone H3.2, Histone H3.3, Histone H3.4 (H3T), Histone H3.5, Histone H3.X and Histone H3.Y but have highly conserved sequences differing only by a few amino acids.[5] [6] Histone H3.3 has been found to play an important role in maintaining genome integrity during mammalian development.[7] Histone variants from different organisms, their classification and variant specific features can be found in "HistoneDB - with Variants" database.

Genetics

Histone H3s are coded by several genes in the human genome, including:

See also

Notes and References

  1. Bhasin M, Reinherz EL, Reche PA . Recognition and classification of histones using support vector machine . Journal of Computational Biology . 13 . 1 . 102–12 . 2006 . 16472024 . 10.1089/cmb.2006.13.102 .
  2. Book: Hartl . Daniel L. . Freifelder . David . Snyder . Leon A. . vanc . 1988 . Basic Genetics . Boston . Jones and Bartlett Publishers . 978-0-86720-090-4 . registration .
  3. Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ . Determination of enriched histone modifications in non-genic portions of the human genome . BMC Genomics . 10 . 143 . March 2009 . 19335899 . 2667539 . 10.1186/1471-2164-10-143 . free .
  4. Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T . Mar 2001 . Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins . Nature . 410 . 6824 . 116–20 . 2001Natur.410..116L . 10.1038/35065132 . 11242053 . 4331863.
  5. Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ . Nov 2002 . The human and mouse replication-dependent histone genes . Genomics . 80 . 5 . 487–98 . 10.1016/S0888-7543(02)96850-3 . 12408966.
  6. Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF . Expression patterns and post-translational modifications associated with mammalian histone H3 variants . The Journal of Biological Chemistry . 281 . 1 . 559–68 . Jan 2006 . 16267050 . 10.1074/jbc.M509266200 . free .
  7. Jang CW, Shibata Y, Starmer J, Yee D, Magnuson T . Histone H3.3 maintains genome integrity during mammalian development . Genes & Development . 29 . 13 . 1377–92 . Jul 2015 . 26159997 . 10.1101/gad.264150.115 . 4511213.