Repression by Groucho/TLE/Grg proteins: genomic site recruitment generates compacted chromatin in vitro and impairs activator binding in vivo.
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.
Sekiya
Takashi
T
Cell and Developmental Biology Program, Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
Zaret
Kenneth S
KS
D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016466:CHO Cells; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D042002:Chromatin Assembly and Disassembly; D006224:Cricetinae; D003412:Cricetulus; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004742:Enhancer Elements, Genetic; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000378:metabolism; D051542:Hepatocyte Nuclear Factor 3-beta / Q000378:metabolism; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D051379:Mice; D009690:Nucleic Acid Conformation; D009707:Nucleosomes / Q000378:metabolism; D011401:Promoter Regions, Genetic; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D011994:Recombinant Proteins / Q000378:metabolism; D012097:Repressor Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D051792:Basic Helix-Loop-Helix Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D051541:Hepatocyte Nuclear Factor 3-alpha; D051542:Hepatocyte Nuclear Factor 3-beta; D018398:Homeodomain Proteins; D009707:Nucleosomes; D011994:Recombinant Proteins; D012097:Repressor Proteins