Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification Journal Article

   

Authors:	Samstein, R. M.; Arvey, A.; Josefowicz, S. Z.; Peng, X.; Reynolds, A.; Sandstrom, R.; Neph, S.; Sabo, P.; Kim, J. M.; Liao, W.; Li, M. O.; Leslie, C.; Stamatoyannopoulos, J. A.; Rudensky, A. Y.
Article Title:	Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification
Abstract:	Regulatory T (Treg) cells, whose identity and function are defined by the transcription factor Foxp3, are indispensable for immune homeostasis. It is unclear whether Foxp3 exerts its Treg lineage specification function through active modification of the chromatin landscape and establishment of new enhancers or by exploiting a pre-existing enhancer landscape. Analysis of the chromatin accessibility of Foxp3-bound enhancers in Treg and Foxp3-negative T cells showed that Foxp3 was bound overwhelmingly to preaccessible enhancers occupied by its cofactors in precursor cells or a structurally related predecessor. Furthermore, the bulk of Foxp3-bound Treg cell enhancers lacking in Foxp3 - CD4 + cells became accessible upon T cell receptor activation prior to Foxp3 expression, and only a small subset associated with several functionally important genes were exclusively Treg cell specific. Thus, in a late cellular differentiation process, Foxp3 defines Treg cell functionality in an "opportunistic" manner by largely exploiting the preformed enhancer network instead of establishing a new enhancer landscape. © 2012 Elsevier Inc.
Keywords:	controlled study; protein expression; human cell; nonhuman; transcription factor foxp3; forkhead transcription factors; animal cell; mouse; animals; mice; cell function; cell structure; protein binding; genetic association; cell differentiation; cell lineage; cell specificity; stem cell; t lymphocyte receptor; regulatory t lymphocyte; lymphocyte activation; t-lymphocytes, regulatory; chromatin; nucleotide sequence; cd4+ t lymphocyte; cd4-positive t-lymphocytes; homeostasis; cell activation; t lymphocyte subpopulation; protein modification; enhancer elements, genetic; landscape; specific pathogen-free organisms
Journal Title:	Cell
Volume:	151
Issue:	1
ISSN:	0092-8674
Publisher:	Cell Press
Date Published:	2012-09-28
Start Page:	153
End Page:	166
Language:	English
DOI:	10.1016/j.cell.2012.06.053
PROVIDER:	scopus
PUBMED:	23021222
PMCID:	PMC3493256
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-84866975037&partnerID=40&md5=2a2e992ffab19c5b4ea9717df4b8c4ef
Notes:	--- - "Export Date: 2 November 2012" - "CODEN: CELLB" - "Molecular Sequence Numbers: GENBANK: GSE40686" - "Source: Scopus"

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