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

Research output: Contribution to journalArticle

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.

Details

Authors
  • Hiroyuki Hosokawa
  • Jonas Ungerbäck
  • Xun Wang
  • Masaki Matsumoto
  • Keiichi I. Nakayama
  • Sarah M. Cohen
  • Tomoaki Tanaka
  • Ellen V. Rothenberg
Organisations
External organisations
  • California Institute of Technology
  • Kyushu University
  • Chiba University
  • Japan Agency for Medical Research and Development
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Immunology in the medical area

Keywords

  • DNA accessibility, repression, Runx1, Satb1, Spi1
Original languageEnglish
Pages (from-to)1119-1134.e7
JournalImmunity
Volume48
Issue number6
Early online date2018 Jan 1
Publication statusPublished - 2018 Jun
Publication categoryResearch
Peer-reviewedYes