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Histone deacetylases (HDAC)

Genomics

See Also

• DNA
• Base pair
• CpG sites
• Epigenetics
• Histone
• Histone methyltransferases (HMT)
• Maternal effect
• Methylation
• Methylenetetrahydrofolate reductase (MTHFR) polymorphism
• Nucleotide
• p53
• Phenotypic plasticity
• SIRT1
• 5,10-methylenetetrahydrofolate reductase (MTHFR)

Description

Histone deacetylases (HDAC) (EC number 3.5.1) are a class of enzymes that remove acetyl groups from an ε-N-acetyl lysine amino acid on a histone. Deacetylation restores a positive electric charge, which increases the histone's affinity for DNA. This generally down-regulates DNA transcription by blocking the access of transcription factors.

Discussion

HDAC inhibitors are being studied as a treatment for cancer. Richon et al. ({{Richon VM, Sandhoff TW, Rifkind RA, Marks PA. AUG 29 2000. "Histone deacetylase inhibitor selectively induces p21(WAF1) expression and gene-associated histone acetylation." Proceedings of the National Academy of Sciences of the United States of America 97(18):10014-10019.}}) found that HDAC inhibitors can induce p21 (WAF1) expression, a regulator of p53's tumor supressor activity. ({{el-Deiry WS, Tokino T, Velculescu VE, Levy DB, Parsons R, Trent JM, Lin D, Mercer WE, Kinzler KW, Vogelstein B. NOV 19 1993. "WAF1, a potential mediator of p53 tumor suppression." Cell 75(4):817-25.}}) HDACs are involved in the pathway by which the retinoblastoma protein (pRb) suppresses cell proliferation. The pRb protein is part of a complex which attracts HDACs to the chromatin so that it will deacetylate histones. ({{Brehm A, Miska EA, McCance DJ, Reid JL, Bannister AJ, Kouzarides T. 1998 Retinoblastoma protein recruits histone deacetylase to repress transcription. Nature 391(6667):597-601.}})

HDAC inhibitors (HDIs) are also associated with the downregulation of some gene promoters. This could be due to upregulation of other, negative-regulatory proteins, however.

Together with the acetylpolyamine amidohydrolases and the acetoin utilization proteins, the histone deacetylases form an ancient protein superfamily known as the histone deacetylase superfamily. ({{Leipe D.D., Landsman D. Histone deacetylases, acetoin utilization proteins and acetylpolyamine amidohydrolases are members of an ancient protein superfamily. Nucleic Acids Res. 25: 3693-3697 (1997) PubMed 9278492.}}) ({{http://www.ebi.ac.uk/interpro/IEntry?ac=IPR000286}})

Links

Attribution

• This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Histone deacetylase.

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