Class IIa HDACs - new insights into their functions in physiology and pathology

HDAC4, 5, 7 and 9 constitute the classIIa histone deacetylases (HDACs) within the large family of protein deacetylases. ClassIIa HDACs have unique features that distinguish them from other HDACs. They contain an N-terminal domain that is required for their interaction with tissue-specific transcription factors and recruitment to their target genes. The N-terminal domain on classIIa HDACs also bears conserved serine residues that undergo signal-dependent phosphorylation, which brings about nuclear export of the enzymes and de-repression of their targets. One of the most important aspects of classIIa HDACs is their expression in specific tissues and organs within the organism, where they have crucial roles in development and differentiation processes. This review brings up to date our knowledge of the physiological and pathological functions of classIIa HDACs, focusing in particular on the most recent discoveries from invivo studies of mouse model systems.