Chromatin remodeling and T helper subset differentiation.
The T helper subsets Th1 and Th2 regulate specific types of immune responses by producing distinct sets of cytokines. Differentiation of the T helper subsets from their common precursors, naive CD4+ T cells, is induced by antigen stimulation and controlled by various other conditions. Of these conditions, the contributions of the cytokine environment have been the best characterized. The presence of interleukin-4 (IL-4) directs the differentiation towards Th2 cells, whereas IL-12 induces Thl differentiation. The Th2 signature cytokine genes encoding IL-4, IL-13, and IL-5 are clustered, and noncoding regions such as the intergenic region of the IL-4 and IL-13 genes are highly conserved from mice to humans. Alteration of the chromatin structure of this Th2 cytokine cluster region is detected as nuclease-accessible regions specific to Th2 cells. Activation of STAT6 promotes Th2 differentiation by inducing Th2-specific transcription factors, including GATA3. Expression of GATA3 induces Th2 differentiation and enhances the Th2 cell-specific chromatin accessibility, indicating that GATA3 is a key protein that regulates differentiation through chromatin remodeling. T helper subset differentiation provides a good system to study gene expression regulation at the chromatin level.
Miyatake
S
S
Department of Molecular and Developmental Biology, Institute of Medical Science, University of Tokyo, Japan.
Arai
N
N
Arai
K
K
D000483:Alleles; D000818:Animals; D002454:Cell Differentiation; D002843:Chromatin / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D007378:Interleukins / Q000235:genetics; D051379:Mice; D008957:Models, Genetic; D018121:Receptors, Cytokine / Q000235:genetics; D015398:Signal Transduction; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D018418:Th2 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D007378:Interleukins; D018121:Receptors, Cytokine; D014157:Transcription Factors