Multiple levels of transcriptional regulation by PLZF in NKT cell development [MoEx-1_0-st]
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ABSTRACT: To identify genes that PLZF is sufficient to modulate in T cells, we compared CD4+ CD8- (CD4SP) thymocytes that overexpressed PLZF to their wildtype counterparts The transcription factor PLZF 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 NKT 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 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.
ORGANISM(S): Mus musculus
PROVIDER: GSE81770 | GEO | 2016/05/24
SECONDARY ACCESSION(S): PRJNA322521
REPOSITORIES: GEO
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