Class IIa HDACs: From important roles in differentiation to possible implications in tumourigenesis

• Introduction • General concepts on class IIa HDACs - Regulation of subcellular localization - Binding partners - Catalytic activity - Class IIa HDAC orthologues in model organisms • HDAC4 - HDAC4 and differentiation - HDAC4 and cancer • HDAC5 - HDAC5 and differentiation - HDAC5 and cancer • HDAC7 - HDAC7 and vascular endothelium - Is HDAC7 a negative regulator of cell proliferation? - HDAC7 and cancer • HDAC9 - HDAC9 and differentiation - HDAC9 and cancer • Conclusions Histone deacetylases (HDACs) are important regulators of gene expression. Specific structural features and distinct regulative mechanisms rationalize the separation of the 18 different human HDACs into four classes. The class II comprises a heterogeneous group of nuclear and cytosolic HDACs involved in the regulation of several cellular functions, not just limited to transcriptional repression. In particular, HDAC4, 5, 7 and 9 belong to the subclass IIa and share many transcriptional partners, including members of the MEF2 family. Genetic studies in mice have disclosed the fundamental contribution of class IIa HDACs to specific developmental/differentiation pathways. In this review, we discuss about the recent literature, which hints a role of class IIa HDACs in the development, growth and aggressiveness of cancer cells.