Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family.
We have cloned and characterized a human cDNA that belongs to the histone deacetylase family, which we designate as HDAC11. The predicted HDAC11 amino acid sequence reveals an open reading frame of 347 residues with a corresponding molecular mass of 39 kDa. Sequence analyses of the putative HDAC11 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 HDAC11 exist in primate, mouse, Drosophila, and plant. Epitope-tagged HDAC11 protein expressed in mammalian cells displays histone deacetylase activity in vitro. Furthermore, HDAC11'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 HDAC11 transcripts is limited to kidney, heart, brain, skeletal muscle, and testis. Epitope-tagged HDAC11 protein localizes predominantly to the cell nucleus. Co-immunoprecipitation experiments indicate that HDAC11 may be present in protein complexes that also contain HDAC6. These results indicate that HDAC11 is a novel and unique member of the histone deacetylase family and it may have distinct physiological roles from those of the known HDACs.
Gao
Lin
L
Department of Oncology, Novartis Pharmaceuticals Corporation, Summit, New Jersey 07901, USA.
Cueto
Maria A
MA
Asselbergs
Fred
F
Atadja
Peter
P
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006655:Histone Deacetylases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D009687:Nuclear Proteins; D012333:RNA, Messenger; C462506:HDAC11 protein, human; D006655:Histone Deacetylases