Calcium Regulation of Myogenesis by Differential Calmodulin Inhibition of Basic Helix-Loop-Helix Transcription Factors
- 1 June 2008
- journal article
- research article
- Published by American Society for Cell Biology (ASCB) in Molecular Biology of the Cell
- Vol. 19 (6), 2509-2519
- https://doi.org/10.1091/mbc.e07-09-0886
Abstract
The members of the MyoD family of basic helix-loop-helix (bHLH) transcription factors are critical regulators of skeletal muscle differentiation that function as heterodimers with ubiquitously expressed E-protein bHLH transcription factors. These heterodimers must compete successfully with homodimers of E12 and other E-proteins to enable myogenesis. Here, we show that E12 mutants resistant to Ca2+-loaded calmodulin (CaM) inhibit MyoD-initiated myogenic conversion of transfected fibroblasts. Ca2+channel blockers reduce, and Ca2+stimulation increases, transcription by coexpressed MyoD and wild-type E12 but not CaM-resistant mutant E12. Furthermore, CaM-resistant E12 gives lower MyoD binding and higher E12 binding to a MyoD-responsive promoter in vivo and cannot rescue myogenic differentiation that has been inhibited by siRNA against E12 and E47. Our data support the concept that Ca2+-loaded CaM enables myogenesis by inhibiting DNA binding of E-protein homodimers, thereby promoting occupancy of myogenic bHLH protein/E-protein heterodimers on promoters of myogenic target genes.Keywords
This publication has 46 references indexed in Scilit:
- B-cell receptor activation inhibits AID expression through calmodulin inhibition of E-proteinsProceedings of the National Academy of Sciences of the United States of America, 2008
- E2A protein degradation by the ubiquitin-proteasome system is stage-dependent during muscle differentiationOncogene, 2006
- MyoD Synergizes with the E-Protein HEBβ To Induce Myogenic DifferentiationMolecular and Cellular Biology, 2006
- Mouse Brain Organization Revealed Through Direct Genome-Scale TF Expression AnalysisScience, 2004
- The role of class I HLH genes in neural development—have they been overlooked?BioEssays, 2003
- Calmodulin-dependent Kinase II Mediates T Cell Receptor/CD3- and Phorbol Ester-induced Activation of IκB KinasePublished by Elsevier BV ,2001
- HDAC4 deacetylase associates with and represses the MEF2 transcription factorThe EMBO Journal, 1999
- The Transcriptional Program in the Response of Human Fibroblasts to SerumScience, 1999
- Restricted Expression of E2A Protein in Primary Human Tissues Correlates with Proliferation and DifferentiationThe American Journal of Pathology, 1998
- HLH forced dimers: Tethering MyoD to E47 generates a dominant positive myogenic factor insulated from negative regulation by IdCell, 1993