Regulation of kidney development by histone deacetylases.

ABSTRACT

There is accumulating evidence that gene expression can be regulated independently of DNA sequence changes, also called epigenetic modifications. Histone deacetylases (HDACs), a specific epigenetic group of enzymes, dynamically and reversibly removes acetyl groups from histone tails projecting from the nucleosome. Clinically, valproic acid fetopathy sheds some insight into the effects of altered HDACs on human embryonic development, since valproic acid is an antiepileptic drug and an HDAC inhibitor. The fetal anomalies include severe renal dysgenesis, supporting the role played by HDACs in human kidney development. Our recent studies have shown that HDACs regulate the transcriptional networks required for controlling the cell cycle, Wnt signaling, and the pathway upstream of the GDNF/RET signaling pathway in the developing kidney. Here, we describe novel HDAC target genes not previously implicated in renal development based on studies using genome-wide microarrays. These genes can be divided into transcription factors, modulators of matrix biology, chromatin remodelers, and DNA repair genes. We also report that HDACs are requisite for tissue-specific gene expression.