Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family

Abstract

We have cloned and characterized a human cDNA that belongs to the histone deacetylase family, which we designate as HDACll. The predicted HDACll amino acid sequence reveals an open reading frame of 347 residues with a corresponding molecular mass of 39 kDa. Sequence analyses of the putative HDACll protein indicate that it contains conserved residues in the catalytic core regions shared by both class I and II mammalian HDAC enzymes. Putative orthologues of HDACll exist in primate, mouse, Drosophila, and plant. Epitopetagged HDACll protein expressed in mammalian cells displays histone deacetylase activity in vitro. Furthermore, HDACll's enzymatic activity is inhibited by trapoxin, a known histone deacetylase inhibitor. Multiple tissue Northern blot and real-time PCR experiments show that the high expression level of HDACll transcripts is limited to kidney, heart, brain, skeletal muscle, and testis. Epitope-tagged HDACll protein localizes predominantly to the cell nucleus. Co-immunoprecipitation experiments indicate that HDACll may be present in protein complexes that also contain HDAC6. These results indicate that HDACll is a novel and unique member of the histone deacetylase family and it may have distinct physiological roles from those of the known HDACs.