[PDF][PDF] Repression by Groucho/TLE/Grg proteins: genomic site recruitment generates compacted chromatin in vitro and impairs activator binding in vivo

T Sekiya, KS Zaret - Molecular cell, 2007 - cell.com
T Sekiya, KS Zaret
Molecular cell, 2007cell.com
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 …
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.
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