Cloning and Functional Characterization of HDAC11, a Novel Member of the Human Histone Deacetylase Family*

By Lin Gao, M. Cueto, F. Asselbergs, P. Atadja. Journal of Biological Chemistry, 2002

757 citations recorded by the source corpus.

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.

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Citations in the corpus

• The Rpd3/Hda1 family of lysine deacetylases: from bacteria and yeast to mice and men (2008, background): “The class IV member HDAC11 shows sequence similarity to class I and II HDAC”
• Sirtuins in aging and age-related disease. (2006, background): “Human HDAC11, the sole member of class IV, is conserved in mice and D. melanogaster but not C. elegans and yeast (Gao et al., 2002).”
• Erasers of histone acetylation: the histone deacetylase enzymes. (2014, methodology): “It uniquely shares sequence homology with the catalytic domains of both Class I and II HDACs, and was first discovered by Basic Local Alignment Search Tool searches of GenBank databases using the yeast Hos3 protein as the query sequence (Gao et al. 2002).”
• Molecular evolution of the histone deacetylase family: functional implications of phylogenetic analysis. (2004, background): “6,8,27,28 However, Figure 2 indicates that HDACs in the sequenced eukaryotic organisms fall cleanly into three (not two) equally distinct groups: the class 1 HDACs, class 2 HDACs, and a group of proteins similar to human HDAC11.”
• Histone deacetylase inhibitors: molecular mechanisms of action (2007, background): “Class IV HDAC is represented by HDAC11, which, like yeast Hda 1 similar 3, has conserved residues in the catalytic core region shared by both class I and II enzymes (Gao et al., 2002).”
• Structural snapshots of human HDAC8 provide insights into the class I histone deacetylases. (2004, background): “…et al., 2003).2 Syrrx, Inc. 10410 Science Center Drive Two related classes of eukaryotic zinc-containing HDACs have been recognized based upon sequenceSan Diego, California 92121 similarity: class I (HDAC1, 2, 3, and 8) and class II (HDAC4, 5, 6, 7, 9, and 10) (Johnstone, 2002; Gao et al., 2002).”
• Histone deacetylases 1 and 2 redundantly regulate cardiac morphogenesis, growth, and contractility. (2007, background): “Class IV HDACs, a recently identified family of deacetylases, share homology with human HDAC11 (Gao et al. 2002).”
• Analysis of histone acetyltransferase and histone deacetylase families of Arabidopsis thaliana suggests functional diversification of chromatin modification among multicellular eukaryotes. (2002, background): “Class III includes predicted proteins HDA403 from D.melanogaster, HDA308 from C.elegans and HDAC11, an EST contig from humans (Fig.”
• Therapeutic application of histone deacetylase inhibitors for central nervous system disorders (2008, background): “HDAC11 is predominantly localized in the nucleus; however it co-precipitates with the primarily cytosolic HDAC6 (Ref”