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Publication : Multiple layers of transcriptional regulation by PLZF in NKT-cell development.

First Author  Mao AP Year  2016
Journal  Proc Natl Acad Sci U S A Volume  113
Issue  27 Pages  7602-7
PubMed ID  27325774 Mgi Jnum  J:234275
Mgi Id  MGI:5789665 Doi  10.1073/pnas.1601504113
Citation  Mao AP, et al. (2016) Multiple layers of transcriptional regulation by PLZF in NKT-cell development. Proc Natl Acad Sci U S A 113(27):7602-7
abstractText  The transcription factor PLZF [promyelocytic leukemia zinc finger, encoded by zinc finger BTB domain containing 16 (Zbtb16)] is induced during the development of innate and innate-like lymphocytes to direct their acquisition of a T-helper effector program, but the molecular mechanisms involved are poorly understood. Using biotinylation-based ChIP-seq and microarray analysis of both natural killer T (NKT) cells and PLZF-transgenic thymocytes, we identified several layers of regulation of the innate-like NKT effector program. First, PLZF bound and regulated genes encoding cytokine receptors as well as homing and adhesion receptors; second, PLZF bound and activated T-helper-specific transcription factor genes that in turn control T-helper-specific programs; finally, PLZF bound and suppressed the transcription of Bach2, a potent general repressor of effector differentiation in naive T cells. These findings reveal the multilayered architecture of the transcriptional program recruited by PLZF and elucidate how a single transcription factor can drive the developmental acquisition of a broad effector program.
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