Trends in Genetics
Class II histone deacetylases: versatile regulators
Section snippets
The class IIa HDACs: HDAC4, -5, -7 and -9
HDAC4, -5, -7 and -9 contain a highly conserved C-terminal catalytic domain (∼420 amino acids) homologous to yHDA1 and an N-terminal domain with no similarity to other proteins (Fig. 1b) 4, 5, 6, 7, 13. MITR, a splice variant of HDAC9, consists of only its N-terminus without an HDAC domain. The activity of the class IIa HDACs is regulated at several levels, including tissue-specific gene expression, recruitment of distinct cofactors and nucleocytoplasmic shuttling.
The class IIb HDACs: HDAC6 and HDAC10
Class IIb HDACs are characterized by duplicated HDAC domains, although this duplication is partial in the case of HDAC10 (Fig. 1b). Class IIb HDACs also show some degree of tissue-specific gene expression: HDAC6 is predominantly expressed in testis 13, 83, and HDAC10 is expressed in liver, spleen and kidney 8, 10, 12. Different splice variants are observed for HDAC10, as shown for HDAC3, -7 and -9, suggesting an additional level of regulation by RNA processing. Analysis of the catalytic
Future questions
The purification, cloning and characterization of class II HDACs have provided important insights into how chromatin controls transcription and have revealed unexpected biological functions for acetylation. The past two years have seen the elucidation of discrete biological pathways in which class II HDACs play crucial regulatory roles. Whereas class IIa HDACs are frequently considered functionally redundant, it is likely that further study will reveal discrete biological functions specific for
Acknowledgements
We thank John Carroll and Jack Hull for graphics, and Stephen Ordway and Gary Howard for editorial assistance. We thank colleagues for sharing unpublished observations and apologize to those whose work could not be cited due to space constraints. Our work is supported by the NIH, The Sandler Foundation and the J. David Gladstone Institutes.
References (90)
Review: chromatin structural features and targets that regulate transcription
J. Struct. Biol.
(2000)Acetylation and chromosomal functions
Curr. Opin. Cell Biol.
(2000)A new family of human histone deacetylases related to Saccharomyces cerevisiae HDA1p
J. Biol. Chem.
(1999)Molecular cloning and characterization of a novel histone deacetylase HDAC10
J. Biol. Chem.
(2002)Isolation and characterization of a novel class II histone deacetylase, HDAC10
J. Biol. Chem.
(2002)Cloning and functional characterization of HDAC11, a novel member of the human histone deacetylase family
J. Biol. Chem.
(2002)Isolation and characterization of mammalian HDAC10, a novel histone deacetylase
J. Biol. Chem.
(2002)Identification of a new family of higher eukaryotic histone deacetylases. Coordinate expression of differentiation-dependent chromatin modifiers
J. Biol. Chem.
(1999)Human HDAC7 histone deacetylase activity is associated with HDAC3 in vivo
J. Biol. Chem.
(2001)CtBP, an unconventional transcriptional co-repressor in development and oncogenesis
Mol. Cell
(2002)
Association of COOH-terminal-binding protein (CtBP) and MEF2-interacting transcription repressor (MITR) contributes to transcriptional repression of the MEF2 transcription factor
J. Biol. Chem.
Mechanism for nucleocytoplasmic shuttling of histone deacetylase 7
J. Biol. Chem.
Calcium regulates transcriptional repression of myocyte enhancer factor 2 by histone deacetylase 4
J. Biol. Chem.
Components of the SMRT co-repressor complex exhibit distinctive interactions with the POZ domain oncoproteins PLZF, PLZF-RARα, and BCL-6
J. Biol. Chem.
BCL-6 represses genes that function in lymphocyte differentiation, inflammation, and cell cycle control
Immunity
Class II histone deacetylases are directly recruited by BCL6 transcriptional repressor
J. Biol. Chem.
SUMO-1 modification of histone deacetylase 1 (HDAC1) modulates its biological activities
J. Biol. Chem.
A dynamic role for HDAC7 in MEF2-mediated muscle differentiation
J. Biol. Chem.
The modular nature of histone deacetylase HDAC4 confers phosphorylation-dependent intracellular trafficking
J. Biol. Chem.
14-3-3 proteins: regulation of subcellular localization by molecular interference
Cell. Signal.
Class II histone deacetylases act as signal-responsive repressors of cardiac hypertrophy
Cell
Regulation of skeletal myogenesis by association of the MEF2 transcription factor with class II histone deacetylases
Mol. Cell
Enzymatic activity associated with class II HDACs is dependent on a multiprotein complex containing HDAC3 and SMRT/N-CoR
Mol. Cell
The N-CoR-HDAC3 nuclear receptor co-repressor complex inhibits the JNK pathway through the integral subunit GPS2
Mol. Cell
The human Sir2 ortholog, hSIRT2, is an NAD+-dependent tubulin deacetylase
Mol. Cell
MEF2: a calcium-dependent regulator of cell division, differentiation and death
Trends Biochem. Sci.
Calcineurin enhances MEF2 DNA binding activity in calcium-dependent survival of cerebellar granule neurons
J. Biol. Chem.
Control of muscle development by dueling HATs and HDACs
Curr. Opin. Genet. Dev.
mHDA1/HDAC5 histone deacetylase interacts with and represses MEF2A transcriptional activity
J. Biol. Chem.
Nerve growth factor induces a gene homologous to the glucocorticoid receptor gene
Neuron
Ca(2+)-dependent gene expression mediated by MEF2 transcription factors
J. Biol. Chem.
Cabin1 represses MEF2-dependent Nur77 expression and T cell apoptosis by controlling association of histone deacetylases and acetylases with MEF2
Immunity
Active maintenance of mHDA2/mHDAC6 histone-deacetylase in the cytoplasm
Curr. Biol.
Microarray deacetylation maps determine genome-wide functions for yeast histone deacetylases
Cell
The emerging role of class II histone deacetylases
Biochem. Cell Biol.
Three proteins define a class of human histone deacetylases related to yeast Hda1p
Proc. Natl. Acad. Sci. U. S. A.
HDAC4 deacetylase associates with and represses the MEF2 transcription factor
EMBO J.
HDAC4, a human histone deacetylase related to yeast HDA1, is a transcriptional co-repressor
Mol. Cell. Biol.
Identification of HDAC10, a novel class II human histone deacetylase containing a leucine-rich domain
Nucleic Acids Res.
Identification of a transcriptional repressor related to the noncatalytic domain of histone deacetylases 4 and 5
Proc. Natl. Acad. Sci. U. S. A.
Cloning and characterization of a histone deacetylase, HDAC9
Proc. Natl. Acad. Sci. U. S. A.
Isolation of a novel histone deacetylase reveals that class I and class II deacetylases promote SMRT-mediated repression
Genes Dev.
Regulation of histone deacetylase 4 and 5 and transcriptional activity by 14-3-3-dependent cellular localization
Proc. Natl. Acad. Sci. U. S. A.
Regulation of histone deacetylase 4 by binding of 14-3-3 proteins
Mol. Cell. Biol.
Activation of the myocyte enhancer factor-2 transcription factor by calcium/calmodulin-dependent protein kinase-stimulated binding of 14-3-3 to histone deacetylase 5
Proc. Natl. Acad. Sci. U. S. A.
Cited by (564)
Various epigenetic regulators
2023, Transcription and Translation in Health and DiseaseThe emerging roles of HDACs and their therapeutic implications in cancer
2022, European Journal of PharmacologyYeast beta-glucan mediates histone deacetylase 5-induced angiogenesis in vascular endothelial cells
2022, International Journal of Biological Macromolecules