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

Hiroyuki Hosokawa, Jonas Ungerbäck, Xun Wang, Masaki Matsumoto, Keiichi Nakayama, Sarah M. Cohen, Tomoaki Tanaka, Ellen V. Rothenberg

Research output: Contribution to journalArticle

11 Citations (Scopus)

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. Transcription factors regulate target genes via sequence-specific DNA binding. They may collaborate when bound together, but are assumed to be independent at sites where they bind alone. Hosokawa, Ungerbäck et al. show that PU.1 broadly shifts the genome-wide site choice of Runx1 DNA binding, enabling PU.1 to repress some target genes at a distance.

Original languageEnglish
Pages (from-to)1119-1134.e7
JournalImmunity
Volume48
Issue number6
DOIs
Publication statusPublished - Jun 19 2018

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Transcription Factors
T-Lymphocytes
Gene Expression
Genes
Binding Sites
Theft
DNA
Genome
Cell Line
proto-oncogene protein Spi-1

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Infectious Diseases

Cite this

Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding. / Hosokawa, Hiroyuki; Ungerbäck, Jonas; Wang, Xun; Matsumoto, Masaki; Nakayama, Keiichi; Cohen, Sarah M.; Tanaka, Tomoaki; Rothenberg, Ellen V.

In: Immunity, Vol. 48, No. 6, 19.06.2018, p. 1119-1134.e7.

Research output: Contribution to journalArticle

Hosokawa, Hiroyuki ; Ungerbäck, Jonas ; Wang, Xun ; Matsumoto, Masaki ; Nakayama, Keiichi ; Cohen, Sarah M. ; Tanaka, Tomoaki ; Rothenberg, Ellen V. / Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding. In: Immunity. 2018 ; Vol. 48, No. 6. pp. 1119-1134.e7.
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