title: Keeping things quiet: roles of NuRD and Sin3 co-repressor complexes during mammalian development.
abstract: Gene inactivation studies of mammalian histone and DNA-modifying proteins have demonstrated a role for many such proteins in embryonic development. Post-implantation embryonic lethality implies a role for epigenetic factors in differentiation and in development of specific lineages or tissues. However a handful of chromatin-modifying enzymes have been found to be required in pre- or peri-implantation embryos. This is significant as implantation is the time when inner cell mass cells of the blastocyst exit pluripotency and begin to commit to form the various lineages that will eventually form the adult animal. These observations indicate a critical role for chromatin-modifying proteins in the earliest lineage decisions of mammalian development, and/or in the formation of the first embryonic cell types. Recent work has shown that the two major class I histone deacetylase-containing co-repressor complexes, the NuRD and Sin3 complexes, are both required at peri-implantation stages of mouse development, demonstrating the importance of histone deacetylation in cell fate decisions. Over the past 10 years both genetic and biochemical studies have revealed surprisingly divergent roles for these two co-repressors in mammalian cells. In this review we will summarise the evidence that the two major class I histone deacetylase complexes in mammalian cells, the NuRD and Sin3 complexes, play important roles in distinct aspects of embryonic development.
authors.affiliation: University of Edinburgh, Edinburgh EH9 3JQ, UK.
authors.forename: Patrick
authors.initials: P
authors.lastname: McDonel
authors.forename: Ita
authors.initials: I
authors.lastname: Costello
authors.forename: Brian
authors.initials: B
authors.lastname: Hendrich
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D049109:Cell Proliferation; D047108:Embryonic Development / Q000235:genetics; D018507:Gene Expression Regulation, Developmental; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008322:Mammals / Q000196:embryology; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D051379:Mice; D008954:Models, Biological; D056264:Sin3 Histone Deacetylase and Corepressor Complex; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D014158:Transcription, Genetic
chemical_list: D006655:Histone Deacetylases; D056245:Mi-2 Nucleosome Remodeling and Deacetylase Complex; D056264:Sin3 Histone Deacetylase and Corepressor Complex
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