ARTICLE | Cover Story

BET-ting on bromodomains

October 21, 2010 7:00 AM UTC

Although histone deacetylases are well-trodden, validated targets,1 the therapeutic potential of inhibiting other aspects of the histone acetylation machineryhas remained an open question. Now, a team led by the Dana-Farber Cancer Institute and the Structural Genomics Consortium has identified a selective inhibitor of bromodomains-protein domains that bind and recognizehistone acetylation-and hasshown its activity in a preclinical model of a rare cancer.

Addition of an acetyl group to lysine residues on histones is an epigenetic mark associated with gene activation. These acetyl groups are reversibly maintainedby histone acetyltransferases (HATs) and histone deacetylases (HDACs).2...