Biomedical subjects

T Mohun

Publications and source records attributed to T Mohun.

3 recordsLinked to original sources

PubMed1992

Muscle differentiation.

Recent studies indicate that vertebrate skeletal muscle originates from two distinct populations of muscle precursor cells formed in early embryogenesis. Divergent patterns of expression for the myoD family of myogenic regulatory genes in different vertebrate embryos suggest some functional redundancy amongst the myogenic factors. Initial gene knockout experiments in mice support this view. Systematic mutagenesis has identified a conserved motif in the basic region of these proteins that is necessary for their biological activity. Direct interaction of both MyoD and myogenin with the transcription factor Jun indicates a mechanism for integrating the control of myoblast growth and differentiation.

Animals↗

PubMed1989

Muscle-specific (CArG) and serum-responsive (SRE) promoter elements are functionally interchangeable in Xenopus embryos and mouse fibroblasts.

The Xenopus cardiac actin gene contains four copies of a promoter element, the CArG box, which is conserved amongst striated muscle actin genes and is essential for tissue-specific expression in the developing Xenopus embryo. Our aim is to identify embryo and muscle proteins that interact with the CArG box as a step towards understanding the molecular basis of this developmentally regulated gene expression. The CArG box shares some sequence similarity with the Serum Response Element (SRE), which mediates the transcriptional activation by serum of genes such as c-fos and cytoskeletal actin. We show here that the most proximal cardiac actin CArG box is recognized by the same binding activity as the cytoskeletal actin SRE in nuclear extracts from both Xenopus embryos and mammalian muscle cells. This activity is indistinguishable from the previously characterized HeLa cell SRE-binding activity, Serum Response Factor (SRF). Importantly, we extend these in vitro studies to demonstrate that the CArG box and SRE are functionally interchangeable, both in Xenopus embryos and mouse fibroblasts. This implies that the CArG box and SRE can bind the same protein in vivo, as well as in vitro. Our results identify an SRF-like protein as a CArG box-binding factor and we discuss the implication that a common mechanism may be utilized in both muscle-specific gene expression and serum-responsive transcription.

Actins↗

PubMed1988

A third striated muscle actin gene is expressed during early development in the amphibian Xenopus laevis.

During early embryonic development in the frog Xenopus laevis, several muscle-specific actin genes encoding distinct actin protein isoforms are activated in cells of the embryonic muscle. In addition to the cardiac (or alpha 1) and skeletal (or alpha 2) actin genes, a third muscle-specific actin gene is expressed in the same embryonic tissue. We have determined the complete nucleotide sequence of this third gene and examined its expression in embryonic and adult tissues. During embryogenesis, this femoral (alpha 3) actin gene is activated several hours later than its cardiac and skeletal counterparts and its transcripts are first detected after neurulation. The gene encodes a skeletal-type actin protein and is expressed exclusively in skeletal muscle in the adult frog. Two copies of this gene have been isolated from the tetraploid species Xenopus laevis, differing by only a few nucleotides in their protein-coding sequence. The related, diploid species, Xenopus tropicalis, possesses a single copy of the alpha 3 gene and its transcript is similarly conserved in nucleotide sequence. However, the X. tropicalis gene is expressed exclusively in embryonic stages of development. Comparison of the X. laevis and X. tropicalis alpha 3 gene promoters reveals extensive sequence homology, including several copies of a repeated motif that is common to other vertebrate striated-muscle actin gene promoters.

Actins↗