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Immunity. 2018 Jun 19;48(6):1119-1134.e7. doi: 10.1016/j.immuni.2018.04.024.

Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding.

Author information

1
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, USA.
2
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, USA; Division of Molecular Hematology, Lund University, Sweden.
3
Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, Japan.
4
Department of Molecular Diagnosis, Graduate School of Medicine, Chiba University, Japan; AMED-CREST, AMED, Japan Agency for Medical Research and Development, Tokyo, Japan.
5
Division of Biology & Biological Engineering, California Institute of Technology, Pasadena, CA, USA. Electronic address: evroth@its.caltech.edu.

Abstract

Transcription factors normally regulate gene expression through their action at sites where they bind to DNA. However, the balance of activating and repressive functions that a transcription factor can mediate is not completely understood. Here, we showed that the transcription factor PU.1 regulated gene expression in early T cell development both by recruiting partner transcription factors to its own binding sites and by depleting them from the binding sites that they preferred when PU.1 was absent. The removal of partner factors Satb1 and Runx1 occurred primarily from sites where PU.1 itself did not bind. Genes linked to sites of partner factor "theft" were enriched for genes that PU.1 represses despite lack of binding, both in a model cell line system and in normal T cell development. Thus, system-level competitive recruitment dynamics permit PU.1 to affect gene expression both through its own target sites and through action at a distance.

KEYWORDS:

DNA accessibility; Runx1; Satb1; Spi1; repression

PMID:
29924977
PMCID:
PMC6063530
[Available on 2019-06-19]
DOI:
10.1016/j.immuni.2018.04.024

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