Role of Signal-responsive Class IIa Histone Deacetylases in Regulating Neuronal Activity-dependent Gene Expression
Histone deacetylases (HDACs) act as transcriptional repressors by catalyzing the deacetylation of lysine residues on the N-terminal tails of histones and altering chromatin structure. Mammalian HDACs are grouped into 3 classes, Class I, II, and III based on their homology to known yeast enzymes. The Class II HDACs comprise of two subgroups of Class IIa and Class IIb enzymes. Class IIa histone deacetylases are subject to signal-dependent intracellular trafficking, which has emerged as an important regulatory mechanism for controlling gene expression through associated transcription factors. This chapter reviews our current understanding of the regulation and function of class IIa HDACs in neuronal cells.
KeywordsHistone Deacetylase Nuclear Export Serum Response Factor Cerebellar Granule Neuron Neuronal Gene Expression
Unable to display preview. Download preview PDF.
- Davis, F. J., Gupta, M., Camoretti-Mercado, B., Schwartz, R. J. and Gupta, M. P. (2003) Calcium/calmodulin-dependent protein kinase activates serum response factor transcription activity by its dissociation from histone deacetylase, HDAC4. Implications in cardiac muscle gene regulation during hypertrophy. J. Biol. Chem. 278, 20047–58.PubMedCrossRefGoogle Scholar
- Dequiedt, F., Martin, M., Von Blume, J., Vertommen, D., Lecomte, E., Mari, N., Heinen, M. F., Bachmann, M., Twizere, J. C., Huang, M. C., Rider, M. H., Piwnica-Worms, H., Seufferlein, T. and Kettmann, R. (2006) New Role for hPar-1 Kinases EMK and C-TAK1 in Regulating Localization and Activity of Class IIa Histone Deacetylases. Mol. Cell Biol. 26, 7086–102.PubMedCrossRefGoogle Scholar
- Guan, Z., Giustetto, M., Lomvardas, S., Kim, J. H., Miniaci, M. C., Schwartz, J. H., Thanos, D. and Kandel, E. R. (2002) Integration of long-term-memory-related synaptic plasticity involves bidirectional regulation of gene expression and chromatin structure. Cell 111, 483–93.PubMedCrossRefGoogle Scholar
- Karpinski, B. A., Morle, G. D., Huggenvik, J., Uhler, M. D. and Leiden, J. M. (1992) Molecular cloning of human CREB-2: an ATF/CREB transcription factor that can negatively regulate transcription from the cAMP response element. Proc. Natl. Acad. Sci. USA 89, 4820–4.Google Scholar
- Linseman, D. A., Bartley, C. M., Le, S. S., Laessig, T. A., Bouchard, R. J., Meintzer, M. K., Li, M. and Heidenreich, K. A. (2003) Inactivation of the myocyte enhancer factor-2 repressor histone deacetylase-5 by endogenous Ca(2depolarization-mediated cerebellar granule)//calmodulin-dependent kinase II promotes depolarization-mediated cerebellar granule neuron survival. J. Biol. Chem. 278, 41472–81.PubMedCrossRefGoogle Scholar
- Zhou, X., Richon, V. M., Wang, A. H., Yang, X. J., Rifkind, R. A. and Marks, P. A. (2000) Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras. Proc. Natl. Acad. Sci. USA 97, 14329–33.Google Scholar