A poised chromatin platform for TGF-β access to master regulators Journal Article

   

Authors:	Xi, Q.; Wang, Z.; Zaromytidou, A. I.; Zhang, X. H. F.; Chow Tsang, L. F.; Liu, J. X.; Kim, H.; Barlas, A.; Manova-Todorova, K.; Kaartinen, V.; Studer, L.; Mark, W.; Patel, D. J.; Massague, J.
Article Title:	A poised chromatin platform for TGF-β access to master regulators
Abstract:	Specific chromatin marks keep master regulators of differentiation silent yet poised for activation by extracellular signals. We report that nodal TGF-β signals use the poised histone mark H3K9me3 to trigger differentiation of mammalian embryonic stem cells. Nodal receptors induce the formation of companion Smad4-Smad2/3 and TRIM33-Smad2/3 complexes. The PHD-Bromo cassette of TRIM33 facilitates binding of TRIM33-Smad2/3 to H3K9me3 and H3K18ac on the promoters of mesendoderm regulators Gsc and Mixl1. The crystal structure of this cassette, bound to histone H3 peptides, illustrates that PHD recognizes K9me3, and Bromo binds an adjacent K18ac. The interaction between TRIM33-Smad2/3 and H3K9me3 displaces the chromatin-compacting factor HP1γ, making nodal response elements accessible to Smad4-Smad2/3 for Pol II recruitment. In turn, Smad4 increases K18 acetylation to augment TRIM33-Smad2/3 binding. Thus, nodal effectors use the H3K9me3 mark as a platform to switch master regulators of stem cell differentiation from the poised to the active state. © 2011 Elsevier Inc.
Keywords:	controlled study; unclassified drug; human cell; promoter region; nonhuman; animal cell; mouse; animals; mice; smad2 protein; smad3 protein; transforming growth factor beta; embryo; embryonic stem cell; protein binding; cell differentiation; homeodomain proteins; transcription factors; regulatory mechanism; amino acid sequence; molecular sequence data; sequence alignment; chromatin; promoter regions, genetic; nucleotide sequence; histone h3; smad proteins; embryonic stem cells; crystal structure; models, molecular; crystallography, x-ray; homeodomain protein; histones; chromatin assembly and disassembly; acetylation; heterochromatin protein 1; smad4 protein; peptides and proteins; goosecoid protein; tripartite motif protein 33
Journal Title:	Cell
Volume:	147
Issue:	7
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2011-12-23
Start Page:	1511
End Page:	1524
Language:	English
DOI:	10.1016/j.cell.2011.11.032
PROVIDER:	scopus
PUBMED:	22196728
PMCID:	PMC3582033
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84455167662&partnerID=40&md5=bd8d0725b88b5fe1015ad55cc531dda0
Notes:	--- - "Export Date: 1 February 2012" - "CODEN: CELLB" - "Source: Scopus"

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