Immunity Resource Discrete Roles of STAT4 and STAT6 Transcription Factors in Tuning Epigenetic Modifications and Transcription during T Helper Cell Differentiation Lai Wei,1,5 Golnaz Vahedi,1,5 Hong-Wei Sun,2 Wendy T. Watford,1 Hiroaki Takatori,1 Haydee L. Ramos,1 Hayato Takahashi,1 Jonathan Liang,1 Gustavo Gutierrez-Cruz,3 Chongzhi Zang,4 Weiqun Peng,4 John J. O’Shea,1 and Yuka Kanno1,* 1Molecular Immunology and Inflammation Branch 2Biodata Mining and Discovery Section 3Laboratory of Muscle Stem Cells and Gene Regulation NIAMS, National Institutes of Health, Bethesda MD 20892, USA 4Department of Physics, George Washington University, Washington, DC 20052, USA 5These authors contributed equally to this work *Correspondence:
[email protected] DOI 10.1016/j.immuni.2010.06.003 SUMMARY constrain immune-mediated damage (Sakaguchi et al., 2008). Thus, the attainment of these cell fates is critical not only for Signal transducer and activator of transcription 4 proper elimination of pathogens, but also for avoidance of (STAT4) and STAT6 are key factors in the specifica- damage to the host (Reiner, 2007). tion of helper T cells; however, their direct roles in The microenvironment of the naive CD4+ T cell greatly influ- driving differentiation are not well understood. Using ences its specification, with a key factor being the cytokine chromatin immunoprecipitation and massive parallel milieu. A major means by which cytokines exert their effect is sequencing, we quantitated the full complement of through activation of signal transducer and activator of transcrip- tion (STAT) family transcription factors, which translocate to the STAT-bound genes, concurrently assessing global nucleus, bind to the regulatory region of genes and induce tran- STAT-dependent epigenetic modifications and scription (Levy and Darnell, 2002; Schindler and Darnell, 1995).