MSX1 inhibits MyoD expression in fibroblast × 10T 1 2 cell hybrids

Paul Woloshin, Kening Song, Catherine Degnin, Ann Mc Neill Killary, David J. Goldhamer, David Sassoon, Mathew J. Thayer

Research output: Contribution to journalArticle

125 Scopus citations

Abstract

Transfer of human chromosome 11, which contains the myoD locus, from primary fibroblasts into 10T 1 2 cells results in activation of myoD. In contrast, hybrids that retain human chromosome 11 and additional human chromosomes fail to activate myoD. We show that human chromosome 4 inhibits myoD activation. myoD enhancer/promoter reporter constructs show that repression is at the transcriptional level. Chromosome fragment-containing hybrids localize the repressing activity to the region of 4p that contains the homeobox gene MSX1. MSX1 is expressed in primary human fibroblasts and in 10T 1 2 cells containing human chromosome 4, while parental 10T 1 2 cells do not express Msx1. Forced expression of Msx1 represses myoD enhancer activity. Msx1 protein binds to the myoD enhancer and likely represses myoD transcription directly. Antisense MSX1 relieves repression mediated by chromosome 4. We conclude that MSX1 inhibits transcription of myoD and that myoD is a target for homeobox gene regulation.

Original languageEnglish (US)
Pages (from-to)611-620
Number of pages10
JournalCell
Volume82
Issue number4
DOIs
StatePublished - Aug 25 1995

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Woloshin, P., Song, K., Degnin, C., Killary, A. M. N., Goldhamer, D. J., Sassoon, D., & Thayer, M. J. (1995). MSX1 inhibits MyoD expression in fibroblast × 10T 1 2 cell hybrids. Cell, 82(4), 611-620. https://doi.org/10.1016/0092-8674(95)90033-0