Human myocyte-specific enhancer factor 2 comprises a group of tissue-restricted MADS box transcription factors.

Abstract

The MEF2 site is an essential element of muscle enhancers and promoters that is bound by a nuclear activity found, so far, only in muscle and required for tissue-specific transcription. We have cloned a group of transcription factors from human muscle that are responsible for this activity: They are present in muscle-specific DNA-binding complexes, have a target sequence specificity identical to that of the endogenous activity, and are MEF2 site-dependent transcriptional activators. These MEF2 proteins comprise several alternatively spliced isoforms from one gene and a related factor encoded by a second gene. All share a conserved amino-terminal DNA-binding domain that includes the MADS homology. MEF2 transcripts are ubiquitous but accumulate preferentially in skeletal muscle, heart, and brain. Specific alternatively spliced isoforms are restricted to these tissues, correlating exactly with the presence of endogenous MEF2 activity. Furthermore, MEF2 protein is detected only in skeletal and cardiac muscle nuclei and not in myoblast and nonmuscle cells. Thus, post-transcriptional regulation is important in the generation of tissue-specific MEF2 activity. Cardiac and smooth, as well as skeletal, muscles contain functionally saturating levels of MEF2 trans-activating factors that are absent in nonmuscle cells. Moreover, MEF2 is induced in nonmuscle cells by MyoD; however, MEF2 alone is insufficient to produce the full muscle phenotype. Implications for the molecular mechanisms of myogenesis are considered.

Myogenesis and MyoD Down-regulate Sp1

“…However, not all muscle genes contain functional E boxes in their regulatory promoter regions, and myogenic bHLH proteins can also activate transcription of muscle-specific genes that lack E boxes in their control regions (3). As expected, from these data, other muscle-specific transcription factors have been described to function as intermediates in the activation of gene expression during myogenesis, such as the M-CAT binding factor (11), and the myocyte enhancer factor 2 (MEF2) (12,13).…”

The GATA-4 transcription factor transactivates the cardiac muscle-specific troponin C promoter-enhancer in nonmuscle cells.

“…Numerous studies have provided evidence for the importance of the skeletal muscle-restricted basic helix-loop-helix and MEF-2 transcription factors in the regulation of skeletal muscle development (7,10,27,35,40,47,48,58,65,80,81). Several lines of evidence now suggest that GATA-4 may play an important role in cardiac muscle development.…”

“…This (7, 10,27,35,48,65,81). Therefore, an understanding of muscle cell development must at some level be based upon elucidating the molecular mechanisms that control lineage-specific gene expression during myogenesis.The recent identification and characterization of the basic helix-loop-helix myogenic transcription factors, including MyoD, myogenin, Myf-5, and MRF-4/herculin/Myf-6, as well as the MEF-2 family of transcription factors has added significantly to our understanding of skeletal myogenesis (8, 9,12,15,18,40,41,43,58,59,76,80). These factors bind to and regulate the expression of many skeletal muscle-specific genes (47,48,64,70).…”

Inflammation in Alzheimer’s Disease and Molecular Genetics: Recent Update

“…The myocyte enhancer factor-2 (MEF2) proteins are members of the MADS (MCM1, agamous, deficiency, serum response factor) family of transcription factors (Naya and Olson 1999;Yu et al 1992). In mammals, MEF2 proteins are encoded by four genes MEF2A, B, C, and D. The four MEF2 isoforms are expressed in overlapped, however, with different patterns, both in the tissues of embryos and adults (Potthoff and Olson 2007).…”