Class I lysine deacetylases promote glucocorticoid-induced transcriptional repression through functional interaction with LSD1.

ABSTRACT: Small molecule inhibitors of lysine deacetylases (KDACs) are approved for clinical use in treatment of several diseases. Nuclear receptors, such as the glucocorticoid receptor (GR) use lysine acetyltransferases (KATs or HATs) and KDACs to regulate transcription through acetylation and deacetylation of protein targets such as histones. Previously we have shown that KDAC1 activity facilitates GR-activated transcription at about half of all cellular target genes. In the current study we examine the role of Class I KDACs in glucocorticoid-mediated repression of gene expression. Inhibition of KDACs through two structurally distinct Class I-selective inhibitors prevented dexamethasone (Dex)-mediated transcriptional repression in a gene-selective fashion. In addition, KDAC activity is also necess

SUBMITTER: Patrick NM 

PROVIDER: S-EPMC5444329 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature