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Mol. Cell. Biol. doi:10.1128/MCB.01203-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Spreading of corepressor linked to action of long-range repressor Hairy

Department of Biochemistry and Molecular Biology, and Genetics Program, Michigan State University, East Lansing, MI 48824-1319

^* To whom correspondence should be addressed. Email: arnosti{at}msu.edu.

	Abstract

Transcriptional repressor proteins play key roles in control of gene expression in development. In the Drosophila embryo, two functional classes of repressors have been described, short-range repressors such as Knirps that locally inhibit the activity of enhancers, and long-range repressors such as Hairy that can dominantly inhibit distal elements. Several long-range repressors interact with the Groucho, a conserved corepressor that is homologous to mammalian TLE proteins. Groucho interacts with histone deacetylases and histone proteins, suggesting that it may effect repression by means of chromatin modification, however it is not known how long-range effects are mediated. Using embryo chromatin immunoprecipitation, we have analyzed a Hairy repressible gene in the embryo during activation and repression. When inactivated, repressors, activators, and co-activators co-occupy the promoter, suggesting that repression is not accomplished by displacement of activators or co-activators. Strikingly, the Groucho co-repressor is found to be recruited to the transcribed region of the gene, contacting a region of several kilobases, concomitant with a loss of histone H3 and H4 acetylation. Groucho has been shown to form higher order complexes in vitro, thus our observations suggest that long-range effects may be mediated by a "spreading" mechanism, modifying chromatin over extensive regions to inhibit transcription.