There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Members of the myocyte enhancer factor-2 (MEF2) family of MADS domain transcription factors cannot induce myogenesis in transfected fibroblasts, but when coexpressed with the myogenic basic-helix-loop-helix (bHLH) proteins MyoD or myogenin they dramatically increase the extent of myogenic conversion above that seen with either myogenic bHLH factor alone. This cooperativity required direct interactions between the DNA-binding domains of MEF2 and the myogenic bHLH factors, but only one of the factors needed a transactivation domain, and only one of the factors needed to be bound to DNA. These interactions allow either factor to activate transcription through the other's binding site and reveal a novel mechanism for indirect activation of gene expression via protein-protein interactions between the DNA-binding domains of heterologous classes of transcription factors.

Related collections

Most cited references 39

Record: found
Abstract: found
Article: not found

The MADS-box family of transcription factors.

P Shore, A D Sharrocks (1995)

The MADS-box family of transcription factors has been defined on the basis of primary sequence similarity amongst numerous proteins from a diverse range of eukaryotic organisms including yeasts, plants, insects, amphibians and mammals. The MADS-box is a conserved motif found within the DNA-binding domains of these proteins and the name refers to four of the originally identified members: MCM1, AG, DEFA and SRF. Several proteins within this family have significant biological roles. For example, the human serum-response factor (SRF) is involved in co-ordinating transcription of the protooncogene c-fos, whilst MCM1 is central to the transcriptional control of cell-type specific genes and the pheromone response in the yeast Saccharomyces cerevisiae. The RSRF/MEF2 proteins comprise a sub-family of this class of transcription factors which are key components in muscle-specific gene regulation. Moreover, in plants, MADS-box proteins such as AG, DEFA and GLO play fundamental roles during flower development. The MADS-box is a contiguous conserved sequence of 56 amino acids, of which 9 are identical in all family members described so far. Several members have been shown to form dimers and consequently two functional regions within the MADS-box have been defined. The N-terminal half is the major determinant of DNA-binding specificity whilst the C-terminal half is necessary for dimerisation. This organisation allows the potential formation of numerous proteins, with subtly different DNA-binding specificities, from a limited number of genes by heterodimerisation between different MADS-box proteins. The majority of MADS-box proteins bind similar sites based on the consensus sequence CC(A/T)6GG although each protein apparently possesses a distinct binding specificity. Moreover, several MADS-box proteins specifically recruit other transcription factors into multi-component regulatory complexes. Such interactions with other proteins appears to be a common theme within this family and play a pivotal role in the regulation of target genes.

0 comments Cited 165 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.

T S Hauschka, M Caudy, Lily Y. Jan … (1989)

A DNA binding and dimerization motif, with apparent amphipathic helices (the HLH motif), has recently been identified in various proteins, including two that bind to immunoglobulin enhancers (E12 and E47). We show here that various HLH proteins can bind as apparent heterodimers to a single DNA motif and also, albeit usually more weakly, as apparent homodimers. The HLH domain can mediate heterodimer formation between either daughterless, E12, or E47 (Class A) and achaete-scute T3 or MyoD (Class B) to form proteins with high affinity for the kappa E2 site in the immunoglobulin kappa chain enhancer. The achaete-scute T3 and MyoD proteins do not form kappa E2-binding heterodimers together, and no active complex with N-myc was evident. The formation of a heterodimer between the daughterless and achaete-scute T3 products may explain the similar phenotypes of mutants at these two loci and the genetic interactions between them. A role of E12 and E47 in mammalian development, analogous to that of daughterless in Drosophila, is likely.

0 comments Cited 138 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Drosophila MEF2, a transcription factor that is essential for myogenesis.

B Bour, Susan Abmayr, Paul Taghert … (1995)

mef2 encodes the only apparent Drosophila homolog of the vertebrate myocyte-specific enhancer factor 2 (MEF2). We show herein that the Drosophila MEF2 protein is expressed throughout the mesoderm following gastrulation. Later in embryogenesis, its expression is maintained in precursors and differentiated cells of the somatic and visceral musculature, as well as the heart. We have characterized genetic deficiencies and EMS-induced point mutations that result in complete loss of MEF2 protein in homozygous mutant embryos. These embryos exhibit a dramatic absence of myosin heavy chain (MHC)-expressing myoblasts and lack differentiated muscle fibers. Examination of earlier events of muscle development indicates that the specification and early differentiation of somatic muscle precursors are not affected because even-skipped-, nautilus-, and beta 3-tubulin-expressing myoblasts are present. However, these partially differentiated cells are unable to undergo further differentiation to form muscle fibers in the absence of mef2. The later aspects of differentiation of the visceral mesoderm and the heart are also disrupted in mef2 mutant embryos, although the specification and early development of these tissues appear unaffected. Midgut morphogenesis is disrupted in the mutant embryos, presumably as a consequence of abnormal development of the visceral mesoderm. In the heart, the cardial cells do not express MHC. These results indicate that MEF2 is required for later aspects of differentiation of the three major types of musculature, which include body wall muscles, gut musculature, and the heart, in the Drosophila embryo.

0 comments Cited 74 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

PubMed ID:: 8548800

ScienceOpen disciplines: Chemistry

Keywords: Amino Acid Sequence,Animals,Base Sequence,Basic Helix-Loop-Helix Transcription Factors,Chromosome Mapping,DNA-Binding Proteins,genetics,Embryonic and Fetal Development,Fibroblasts,physiology,Gene Deletion,Gene Expression Regulation, Developmental,Helix-Loop-Helix Motifs,MEF2 Transcription Factors,Mice,Molecular Sequence Data,Muscles,cytology,embryology,MyoD Protein,Myogenic Regulatory Factors,Myogenin,Point Mutation,Transcription Factors,Transcription, Genetic

Cooperative activation of muscle gene expression by MEF2 and myogenic bHLH proteins.

Read this article at

Abstract

Related collections

Journal of Circulating Biomarkers

Most cited references 39

The MADS-box family of transcription factors.

Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence.

Drosophila MEF2, a transcription factor that is essential for myogenesis.

Author and article information

Journal

Comments

Comment on this article

Similar content 501

Cited by 111

Most referenced authors 298