The Groucho/Transducin-like Enhancer of split Transcriptional Repressors Interact with the Genetically Defined Amino-terminal Silencing Domain of Histone H3*
- From the Center for Neuronal Survival, Montreal Neurological Institute, McGill University, Montreal, Quebec H3A 2B4, Canada
Abstract
Groucho is a transcriptional repressor implicated in Notch signaling and involved in neural development and segmentation in Drosophila. We are investigating the molecular mechanisms underlying the functions of Groucho and its mammalian homologs, the transducin-like Enhancer of split (TLE) proteins. We report that Groucho/TLEs are associated with chromatin in live cells and that they co-purify with isolated histones. Affinity chromatography and far Western blotting studies show further that native Groucho/TLE proteins interact specifically with histone H3 and not with other core histones. This interaction is mediated by the H3 amino-terminal domain previously shown by genetic analysis in yeast to be essential for the role of H3 in transcriptional silencing. We also demonstrate that Groucho/TLEs form oligomeric structures in vivo. These combined findings suggest that transcription complexes containing Groucho/TLEs may associate with chromatin through interactions with the amino terminus of histone H3 and that these interactions may be propagated along the chromosome due to the ability of Groucho/TLEs to participate in higher order structures.
Footnotes
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↵* This work was supported by Grant MRC PG11473 (to S. S.) from the Medical Research Council of Canada and the Human Frontier Science Program Grant RG-490/94.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
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↵‡ Scholar of the Fonds de la Recherche en Sante du Quebec and Killam Scholar of the Montreal Neurological Institute. To whom correspondence should be addressed: Montreal Neurological Institute, 3801, rue University, Montreal, Quebec H3A 2B4, Canada. Tel.: 514-398-3946; Fax: 514-398-1319; E-mail: mdst{at}musica.mcgill.ca.
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↵1 The abbreviations used are: bHLH, basic helix-loop-helix; DTSSP, 3,3′-dithiobis(sulfosuccinimidylpropionate); GST, glutathione S-transferase; HES, Hairy and Enhancer of split-like; PAGE, polyacrylamide gel electrophoresis; TLE, transducin-like Enhancer of split.
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↵2 A. Baratz and S. Stifani, unpublished data.
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↵3 R. Grbavec, R. Lo., Y. Liu, and S. Stifani, manuscript submitted for publication.
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- Received March 5, 1997.
- Revision received July 18, 1997.
