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Updated: Feb 27, 2026

Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Chemical modulators for epigenome reader domains as emerging epigenetic therapies for cancer and inflammation
Nilesh Zaware1, Ming-Ming Zhou1
1Department of Pharmacological Sciences, Icahn School of Medicine at Mt. Sinai, 1425 Madison Avenue, New York, NY 10029, United States.
Abstract:
Site-specific lysine acetylation and methylation on histones are critical post-translational modifications (PTMs) that govern ordered gene transcription in chromatin. Mis-regulation of these histone PTM-mediated processes has been shown to be associated with human diseases. Since the 2010 landmark reports of small molecules (+)-JQ1 and I-BET762 that target the acetyl-lysine 'reader' Bromodomain and Extra Terminal domain (BET) proteins, there have been relentless efforts to develop epigenetic therapy with small molecules to modulate molecular interactions of epigenome reader domain proteins with PTMs. In addition to BET, the other emerging targets include non-BET acetyl-lysine and methyl-lysine reader domains. This review covers the key chemical modulators of the aforementioned epigenome reader proteins.
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