Implications of small molecule activators and inhibitors of histone acetyltransferases in chromatin therapy.
Histone acetylation is a diagnostic feature of transcriptionally active chromatin. The group of enzymes, histone acetyltransferases (HATs), involved in this crucial step of gene regulation, covalently modifies the N-terminal lysine residues of histones by the addition of an acetyl group from acetyl coenzyme A. Dysfunction of these enzymes is often associated with several diseases, ranging from neurodegenerative disorders to cancer. These enzymes thus are potential new targets for therapeutics. We have discovered few small molecule compounds, which target HATs and either activate or inhibit the enzyme potently. These compounds would be useful as biological switching molecules for probing into the role of HATs in gene regulation and cell cycle and may be useful as new chemical entities for the development of new drugs.
Transcription and Disease Laboratory, Molecular Biology and Genetics Unit, Jawaharlal Nehru Centre for Advanced Scientific Research, Jakkur, Bangalore 560064, India.
Radhika A
RA
Varier
V
V
Swaminathan
Karanam
K
Balasubramanyam
Tapas K
TK
Kundu
D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002843:Chromatin / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005544:Forecasting; D051548:Histone Acetyltransferases; D006657:Histones / Q000378:metabolism; D006801:Humans
D002843:Chromatin; D004791:Enzyme Inhibitors; D006657:Histones; D000123:Acetyltransferases; D051548:Histone Acetyltransferases