Title | Foxp3 exploits a pre-existent enhancer landscape for regulatory T cell lineage specification. |
Publication Type | Journal Article |
Year of Publication | 2012 |
Authors | Samstein RM, Arvey A, Josefowicz SZ, Peng X, Reynolds A, Sandstrom R, Neph S, Sabo P, Kim JM, Liao W, Li MO, Leslie C, Stamatoyannopoulos JA, Rudensky AY |
Journal | Cell |
Volume | 151 |
Issue | 1 |
Pagination | 153-66 |
Date Published | 2012 Sep 28 |
ISSN | 1097-4172 |
Keywords | Animals, CD4-Positive T-Lymphocytes, Cell Differentiation, Chromatin, Enhancer Elements, Genetic, Female, Forkhead Box Protein O1, Forkhead Transcription Factors, Lymphocyte Activation, Mice, Specific Pathogen-Free Organisms, T-Lymphocytes, Regulatory |
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. |
DOI | 10.1016/j.cell.2012.06.053 |
Alternate Journal | Cell |
PubMed ID | 23021222 |
Grant List | GM07739 / GM / NIGMS NIH HHS / United States DK091968 / DK / NIDDK NIH HHS / United States 5R37AI034206 / AI / NIAID NIH HHS / United States |
Related Faculty:
Steven Josefowicz, Ph.D.