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Myocyte Enhancer Factor 2A Is Transcriptionally Autoregulated
- Source :
- Journal of Biological Chemistry. 283:10318-10329
- Publication Year :
- 2008
- Publisher :
- Elsevier BV, 2008.
-
Abstract
- MEF2 (myocyte enhancer factor 2) proteins are a small family of transcription factors that play pivotal roles in striated muscle differentiation, development, and metabolism, in neuron survival and synaptic formation, and in lymphocyte selection and activation. Products of the four mammalian MEF2 genes, MEF2A, MEF2B, MEF2C, and MEF2D, are expressed with overlapping but distinct temporospatial patterns. Toward analysis of MEF2A functions and the determinants of its regulated expression, we have mapped and begun studies of the transcriptional control regions of this gene. Heterogeneous 5′-untranslated regions of MEF2A mRNAs result from use of alternative promoters and splicing patterns. The two closely approximated TATA-less promoters are ∼65 kb upstream of the exon containing the sole initiation codon. Ribonuclease protection and primer extension assays show that each promoter is active in various adult tissues. A canonical MEF2 site overlies the major promoter 1 transcription start site. This element specifically binds MEF2 factors, including endogenous nuclear MEF2A according to chromatin immunoprecipitation studies, and is critical to MEF2A transcription in myocytes. The site exerts reciprocal control of the alternative promoters, silencing promoter 1 and activating promoter 2 under some conditions. Erk5 and p38 MAPK signaling stimulate MEF2A expression by activating both promoters from the MEF2 element. MEF2A transcription is therefore subject to positive or negative regulation by its protein products, depending on signaling activities that influence MEF2 factor trans-activity. The sole MEF2 gene of the cephalochordate amphioxus has a similar regulatory region structure, suggesting that this mode of autoregulatory control is conserved among higher metazoan MEF2 genes.
- Subjects :
- Mef2
Transcription, Genetic
Molecular Sequence Data
Response element
Biology
Models, Biological
Biochemistry
Upstream activating sequence
Animals
Humans
Transcription, Chromatin, and Epigenetics
Chordata
Codon
Enhancer
Molecular Biology
Transcription factor
Genetics
Regulation of gene expression
Muscle Cells
Base Sequence
MEF2 Transcription Factors
Calcineurin
Promoter
Cell Biology
Enhancer Elements, Genetic
Gene Expression Regulation
Myogenic Regulatory Factors
5' Untranslated Regions
Chromatin immunoprecipitation
Plasmids
Subjects
Details
- ISSN :
- 00219258
- Volume :
- 283
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry
- Accession number :
- edsair.doi.dedup.....f5c87eeffd8f06106d18481a0f7e5130