HATs off to Hop: recruitment of a class I histone deacetylase incriminates a novel transcriptional pathway that opposes cardiac hypertrophy

Abstract

Histone acetylation, regulated by two antagonistic enzymes - histone acetyltransferases (HATs) and histone deacetylases (HDACs) - results in transcriptional changes and also plays a critical role in cardiac development and disease. A new study shows that overexpression of the atypical transcriptional corepressor homeodomain-only protein (Hop) causes cardiac hypertrophy via recruitment of a class I HDAC. In contrast to the body of work on transcriptional mechanisms that drive cardiac hypertrophy, including class II HDACs, this report elucidates a novel growth-suppressing transcriptional pathway in cardiac muscle that opposes hypertrophic growth.

Figure 1

Complementary functions of class I and class II HDACs in cardiac hypertrophy. (a) The myocyte enhancer factor-2–based transcriptional program that triggers cardiac hypertrophy is repressed by signal-responsive class II HDACs, which are exported from the nucleus as the result of hypertrophic cues (1, 2). (b) A class I HDAC (HDAC2) is recruited to SRF — via Hop as an intermediary — thereby blocking a transcriptional program that opposes hypertrophy (14). MEF2, myocyte enhancer factor-2.