An epigenetic view of helper T cell differentiation.
Antigen and cytokine receptor signals act in synergy to direct the differentiation of CD4+ T cells. These signals initiate reciprocal activation and silencing of the interferon-gamma (IFN-gamma) and interleukin 4 (IL-4) cytokine gene loci, changes that are heritably maintained in the resulting T helper type 1 (T(H)1) or T(H)2 cells and their progeny. Early, unpolarized transcription and chromatin remodeling of the poised cytokine genes of naive T cells is followed by consolidation and spreading of epigenetic changes and the establishment of self-reinforcing transcription factor networks. Recent studies have begun to elucidate the molecular mechanisms that establish and maintain polarized cytokine gene expression, and thus the cellular identity of differentiated helper T cells.
Ansel
K Mark
KM
Center for Blood Research, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA.
Lee
Dong U
DU
Rao
Anjana
A
D000818:Animals; D002454:Cell Differentiation / Q000235:genetics*; D002843:Chromatin / Q000502:physiology; D002874:Chromosome Mapping; D004268:DNA-Binding Proteins / Q000502:physiology; D050990:GATA3 Transcription Factor; D005786:Gene Expression Regulation; D020868:Gene Silencing; D006801:Humans; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D011401:Promoter Regions, Genetic; D006377:T-Lymphocytes, Helper-Inducer / Q000502:physiology*; D015534:Trans-Activators / Q000502:physiology; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D015534:Trans-Activators; D015847:Interleukin-4