The basic helix-loop-helix transcription factor Mist1 functions as a transcriptional repressor of MyoD
Open Access
- 2 March 1998
- journal article
- research article
- Published by Springer Science and Business Media LLC in The EMBO Journal
- Vol. 17 (5), 1412-1422
- https://doi.org/10.1093/emboj/17.5.1412
Abstract
A good model system to examine aspects of positive and negative transcriptional regulation is the muscle‐specific regulatory factor, MyoD, which is a basic helix–loop–helix (bHLH) transcription factor. Although MyoD has the ability to induce skeletal muscle terminal differentiation in a variety of non‐muscle cell types, MyoD activity itself is highly regulated through protein–protein interactions involving several different co‐factors. Here we describe the characterization of a novel bHLH protein, Mist1, and how it influences MyoD function. We show that Mist1 accumulates in myogenic stem cells (myoblasts) and then decreases as myoblasts differentiate into myotubes. Mist1 functions as a negative regulator of MyoD activity, preventing muscle differentiation and the concomitant expression of muscle‐specific genes. Mist1‐induced inhibition occurs through a combination of mechanisms, including the formation of inactive MyoD–Mist1 heterodimers and occupancy of specific E‐box target sites by Mist1 homodimers. Mist1 lacks a classic transcription activation domain and instead possesses an N‐terminal repressor region capable of inhibiting heterologous activators. Thus, Mist1 may represent a new class of repressor molecules that play a role in controlling the transcriptional activity of MyoD, ensuring that expanding myoblast populations remain undifferentiated during early embryonic muscle formation.Keywords
This publication has 38 references indexed in Scilit:
- A complex containing N-CoR, mSln3 and histone deacetylase mediates transcriptional repressionNature, 1997
- Mist1: A Novel Basic Helix-Loop-Helix Transcription Factor Exhibits a Developmentally Regulated Expression PatternDevelopmental Biology, 1997
- Images and Interdependencies: National Military Establishments and the Advancement of Science and Technology . Studies in 20th Century History. Paul Forman and José M. Sánchez Ron, Eds. Kluwer, Norwell, MA, 1996. xiv, 340 pp. $164 or Dfl.245 or £105. ISBN 0-7923-3541-4. Boston Studies in the Philosophy of Science, vol. 180.Science, 1996
- Examination of Mammalian Basic Helix–Loop–Helix Transcription Factors Using a Yeast One-Hybrid SystemDNA and Cell Biology, 1996
- Ligand-independent repression by the thyroid hormone receptor mediated by a nuclear receptor co-repressorNature, 1995
- HLH forced dimers: Tethering MyoD to E47 generates a dominant positive myogenic factor insulated from negative regulation by IdCell, 1993
- The protein Id: A negative regulator of helix-loop-helix DNA binding proteinsCell, 1990
- Fos and Jun bind cooperatively to the AP-1 site: reconstitution in vitro.Genes & Development, 1988
- GAL4-VP16 is an unusually potent transcriptional activatorNature, 1988
- Cytoplasmic activation of human nuclear genes in stable heterocaryonsCell, 1983