Transcriptional and epigenetic control of T helper cell specification: molecular mechanisms underlying commitment and plasticity.
T helper cell differentiation occurs in the context of the extracellular cytokine milieu evoked by diverse microbes and other pathogenic stimuli along with T cell receptor stimulation. The culmination of these signals results in specification of T helper lineages, which occurs through the combinatorial action of multiple transcription factors that establish distinctive transcriptomes. In this manner, inducible, but constitutively active, master regulators work in conjunction with factors such as the signal transducer and activator of transcriptions (STATs) that sense the extracellular environment. The acquisition of a distinctive transcriptome also depends on chromatin modifications that impact key cis elements as well as the changes in global genomic organization. Thus, signal transduction and epigenetics are linked in these processes of differentiation. In this review, recent advances in understanding T helper lineage specification and deciphering the action of transcription factors are summarized with emphasis on comprehensive views of the dynamic T cell epigenome.
Molecular Immunology and Inflammation Branch, National Institutes of Arthritis, and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. kannoy@mail.nih.gov
Yuka
Y
Kanno
Golnaz
G
Vahedi
Kiyoshi
K
Hirahara
Kentner
K
Singleton
John J
JJ
O'Shea
D000818:Animals; D001327:Autoimmune Diseases / Q000235:genetics; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D019070:Cell Lineage / Q000235:genetics; D044127:Epigenesis, Genetic; D057890:Epigenomics; D005786:Gene Expression Regulation; D006801:Humans; D022661:RNA, Untranslated / Q000235:genetics / Q000378:metabolism; D050436:Regulatory Elements, Transcriptional; D006377:T-Lymphocytes, Helper-Inducer / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic
D022661:RNA, Untranslated; D014157:Transcription Factors