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Repression by Groucho/TLE/Grg Proteins: Genomic Site Recruitment Generates Compacted Chromatin In Vitro and Impairs Activator Binding In Vivo

2007; Elsevier BV; Volume: 28; Issue: 2 Linguagem: Inglês

10.1016/j.molcel.2007.10.002

1097-4164

Takashi Sekiya, Kenneth S. Zaret,

Plant Molecular Biology Research

Summary Groucho-related (Gro/TLE/Grg) corepressors meditate embryonic segmentation, dorsal-ventral patterning, neurogenesis, and Notch and Wnt signaling. Although Gro/TLE/Grgs disrupt activator complexes and recruit histone deacetylases (HDAC), activator complexes can be disrupted in various ways, HDAC recruitment does not account for full corepressor activity, and a direct role for Gro/TLE/Grg binding and altering chromatin structure has not been explored. Using diverse chromatin substrates in vitro, we show that Grg3 creates higher-order, condensed complexes of polynucleosome arrays. Surprisingly, such complexes are in an open, exposed configuration. We find that chromatin binding enables Grg3 recruitment by a transcription factor and the creation of a closed, poorly accessible domain spanning three to four nucleosomes. Targeted recruitment of Grg3 blankets a similar-sized region in vivo, impairing activator recruitment and repressing transcription. These activities of a Groucho protein represent a newly discovered mechanism which differs from that of other classes of corepressors.