Journal Article

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

Mao, Ai-Ping, Chen, Xiaoting, Constantinides, Michael G., Zuo, Zhixiang, Weirauch, Matthew T., Mathew, Rebecca, Bendelac, Albert

2016

Overview

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.

• Publisher: National Academy of Sciences
• Subject: Animals / Basic-Leucine Zipper Transcription Factors - metabolism / Biological Sciences / Core Binding Factor alpha Subunits - metabolism / Cytokines - metabolism / Gene Expression Regulation / Immunology and Inflammation / Kruppel-Like Transcription Factors - metabolism / Mice, Inbred C57BL / Mice, Transgenic / Natural Killer T-Cells - physiology / Promyelocytic Leukemia Zinc Finger Protein / Proto-Oncogene Proteins c-ets - metabolism / Receptors, Chemokine - metabolism / T-Lymphocytes, Helper-Inducer - metabolism