|H3 histone, family 3A (H3.3A)|
|Locus||Chr. 1 q41|
|H3 histone, family 3B (H3.3B)|
|Locus||Chr. 17 q25|
Histone H3 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, 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-terminal tail of histone H3 protrudes from the globular nucleosome core and can undergo several different types of 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, while mono-methylation of K4 is associated with active genes. Acetylation of histone H3 occurs at several different lysine positions in the histone tail and is performed by a family of enzymes known as histone acetyltransferases (HATs). Acetylation of lysine14 is commonly seen in genes that are being actively transcribed into RNA.
Mammalian cells have three known sequence variants of histone H3. These are denoted as Histone H3.1, Histone H3.2 and Histone H3.3 but are highly sequence conserved differing only by a few amino acids.
Histone H3s are coded by several genes in the human genome, including:
- H3.1: HIST1H3A, HIST1H3B, HIST1H3C, HIST1H3D, HIST1H3E, HIST1H3F, HIST1H3G, HIST1H3H, HIST1H3I, HIST1H3J
- H3.2: HIST2H3A, HIST2H3C, HIST2H3D
- H3.3: H3F3A, H3F3B
- Bhasin M, Reinherz EL, Reche PA (2006). "Recognition and classification of histones using support vector machine". J. Comput. Biol. 13 (1): 102–12. doi:10.1089/cmb.2006.13.102. PMID 16472024.
- Hartl Daniel L., Freifelder David, Snyder Leon A. (1988). Basic Genetics. Boston: Jones and Bartlett Publishers. ISBN 0-86720-090-1.
- Rosenfeld JA, Wang Z, Schones DE, Zhao K, DeSalle R, Zhang MQ (March 2009). "Determination of enriched histone modifications in non-genic portions of the human genome". BMC Genomics 10: 143. doi:10.1186/1471-2164-10-143. PMC 2667539. PMID 19335899.
- Lachner M, O'Carroll D, Rea S, Mechtler K, Jenuwein T (March 2001). "Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins". Nature 410 (6824): 116–20. doi:10.1038/35065132. PMID 11242053.
- Marzluff WF, Gongidi P, Woods KR, Jin J, Maltais LJ (November 2002). "The human and mouse replication-dependent histone genes". Genomics 80 (5): 487–98. doi:10.1016/S0888-7543(02)96850-3. PMID 12408966.
- Hake SB, Garcia BA, Duncan EM, Kauer M, Dellaire G, Shabanowitz J, Bazett-Jones DP, Allis CD, Hunt DF (January 2006). "Expression patterns and post-translational modifications associated with mammalian histone H3 variants". J. Biol. Chem. 281 (1): 559–68. doi:10.1074/jbc.M509266200. PMID 16267050.