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Published on: March 22, 2017
Myocyte enhancer factor 2A is transcriptionally autoregulated
Bindu Ramachandran1, Gengsheng Yu, Shiguang Li
1Diabetes Research Laboratory, Department of Medicine, Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA.
Myocyte enhancer factor 2A (MEF2A) gene expression is regulated by its own protein products. This autoregulation, involving alternative promoters and signaling pathways, is conserved in evolution.
Area of Science:
- Molecular Biology
- Genetics
- Developmental Biology
Background:
- Myocyte enhancer factor 2 (MEF2) proteins are crucial transcription factors in muscle and neuronal development.
- The MEF2 gene family, including MEF2A, exhibits complex expression patterns.
Purpose of the Study:
- To investigate the transcriptional regulation of the MEF2A gene.
- To identify regulatory elements and signaling pathways controlling MEF2A expression.
Main Methods:
- Mapping of MEF2A transcriptional control regions.
- Ribonuclease protection and primer extension assays to analyze mRNA.
- Chromatin immunoprecipitation to study protein-DNA interactions.
- Analysis of promoter activity under different signaling conditions.
Main Results:
- MEF2A possesses two alternative TATA-less promoters located 65 kb upstream.
- Both promoters are active in adult tissues and are regulated by a MEF2 binding site.
- This MEF2 site autoregulates MEF2A transcription, silencing promoter 1 and activating promoter 2.
- Erk5 and p38 MAPK signaling pathways activate MEF2A expression via the MEF2 element.
- Similar regulatory structures are found in amphioxus MEF2, suggesting evolutionary conservation.
Conclusions:
- MEF2A transcription is subject to autoregulation by MEF2 factors.
- Signaling pathways modulate MEF2A expression through this autoregulatory mechanism.
- The conserved regulatory structure highlights the ancient importance of MEF2A autoregulation.
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