Calcium Regulates Transcriptional Repression of Myocyte Enhancer Factor 2 by Histone Deacetylase 4

• Published in: The Journal of biological chemistry 2000-07, Vol.275 (29), p.22563-22567
• Main Authors: Youn, Hong-Duk, Grozinger, Christina M., Liu, Jun O.
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Cabin1 protein; Calcium - metabolism; calmodulin; Calmodulin - metabolism; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Gene Expression Regulation; HDAC4 protein; Histone Deacetylases - genetics; Histone Deacetylases - metabolism; Humans; Jurkat Cells; MEF2 protein; MEF2 Transcription Factors; MITR protein; Molecular Sequence Data; myocyte enhancer factor 2; Myogenic Regulatory Factors; Signal Transduction; Transcription Factors - genetics; Transcription Factors - metabolism; Transcription, Genetic
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.C000304200

The myocyte enhancer factor 2 (MEF2) consists of a family of transcription factors that play important roles in a number of physiological processes from muscle cell differentiation to neuronal survival and T cell apoptosis. MEF2 has been reported to be associated with several distinct repressors including Cabin1(cain), MEF2-interacting transcriptional repressor (MITR), and HDAC4. It has been previously shown that Cabin1 is associated with MEF2 in a calcium-sensitive manner; activated calmodulin binds to Cabin1 and releases it from MEF2. However, it was not known whether the binding of HDAC4 and MITR to MEF2 is also regulated by calcium. We report that HDAC4 and MITR contain calmodulin-binding domains that overlap with their MEF2-binding domains. Binding of calmodulin to HDAC4 leads to its dissociation from MEF2, relieving MEF2 from the transcriptional repression by HDAC4. Together, HDAC4, MITR, and Cabin1 constitute a family of calcium-sensitive transcriptional repressors of MEF2.