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Mol. Cell. Biol., Feb 1995, 861-871, Vol 15, No. 2
KM Catron, H Zhang, SC Marshall, JA Inostroza, JM Wilson and C Abate
This study investigates the transcriptional properties of Msx-1, a murine
homeodomain protein which has been proposed to play a key role in
regulating the differentiation and/or proliferation state of specific cell
populations during embryogenesis. We show, using basal and activated
transcription templates, that Msx-1 is a potent repressor of transcription
and can function through both TATA-containing and TATA- less promoters.
Moreover, repression in vivo and in vitro occurs in the absence of
DNA-binding sites for the Msx-1 homeodomain. Utilizing a series of
truncated Msx-1 polypeptides, we show that multiple regions of Msx-1
contribute to repression, and these are rich in alanine, glycine, and
proline residues. When fused to a heterologous DNA-binding domain, both N-
and C-terminal regions of Msx-1 retain repressor function, which is
dependent upon the presence of the heterologous DNA- binding site.
Moreover, a polypeptide consisting of the full-length Msx- 1 fused to a
heterologous DNA-binding domain is a more potent repressor than either the
N- or C-terminal regions alone, and this fusion retains the ability to
repress transcription in the absence of the heterologous DNA site. We
further show that Msx-1 represses transcription in vitro in a purified
reconstituted assay system and interacts with protein complexes composed of
TBP and TFIIA (DA) and TBP, TFIIA, and TFIIB (DAB) in gel retardation
assays, suggesting that the mechanism of repression is mediated through
interaction(s) with a component(s) of the core transcription complex. We
speculate that the repressor function of Msx-1 is critical for its proposed
role in embryogenesis as a regulator of cellular differentiation.
Copyright © 1995, American Society for Microbiology
Transcriptional repression by Msx-1 does not require homeodomain DNA- binding sites
Center for Advanced Biotechnology and Medicine, UMDNJ-Robert Wood Johnson Medical School, Piscataway.
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