This Article Full Text Full Text (PDF) Other Versions of this Article: MCB.01203-07v1 28/8/2792    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Google Scholar Articles by Martinez, C. A. Articles by Arnosti, D. N. PubMed PubMed Citation Articles by Martinez, C. A. Articles by Arnosti, D. N.

 Previous Article  |  Next Article 

Molecular and Cellular Biology, April 2008, p. 2792-2802, Vol. 28, No. 8
0270-7306/08/$08.00+0     doi:10.1128/MCB.01203-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Spreading of a Corepressor Linked to Action of Long-Range Repressor Hairy

Carlos A. Martinez and David N. Arnosti^*

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

Received 6 July 2007/ Returned for modification 14 August 2007/ Accepted 4 February 2008

Transcriptional repressor proteins play key roles in the control of gene expression in development. For the Drosophila embryo, the following 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 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 coactivators cooccupy the promoter, suggesting that repression is not accomplished by the displacement of activators or coactivators. Strikingly, the Groucho corepressor 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.

Published ahead of print on 19 February 2008.

Present address: Department of Applied Mathematics and Statistics, Stony Brook University, Stony Brook, NY 11794-3600.