Advanced

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

Hosokawa, Hiroyuki; Ungerbäck, Jonas LU ; Wang, Xun; Matsumoto, Masaki; Nakayama, Keiichi I.; Cohen, Sarah M.; Tanaka, Tomoaki and Rothenberg, Ellen V. (2018) In Immunity 48(6). p.7-1134
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... (More)

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.

(Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
DNA accessibility, repression, Runx1, Satb1, Spi1
in
Immunity
volume
48
issue
6
pages
7 - 1134
publisher
Cell Press
external identifiers
  • scopus:85048158088
ISSN
1074-7613
DOI
10.1016/j.immuni.2018.04.024
language
English
LU publication?
yes
id
f6b89f1b-30c9-4d92-81a6-5fbf4fcaddf4
date added to LUP
2018-06-21 16:21:53
date last changed
2019-04-10 04:10:18
@article{f6b89f1b-30c9-4d92-81a6-5fbf4fcaddf4,
  abstract     = {<p>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.</p>},
  author       = {Hosokawa, Hiroyuki and Ungerbäck, Jonas and Wang, Xun and Matsumoto, Masaki and Nakayama, Keiichi I. and Cohen, Sarah M. and Tanaka, Tomoaki and Rothenberg, Ellen V.},
  issn         = {1074-7613},
  keyword      = {DNA accessibility,repression,Runx1,Satb1,Spi1},
  language     = {eng},
  number       = {6},
  pages        = {7--1134},
  publisher    = {Cell Press},
  series       = {Immunity},
  title        = {Transcription Factor PU.1 Represses and Activates Gene Expression in Early T Cells by Redirecting Partner Transcription Factor Binding},
  url          = {http://dx.doi.org/10.1016/j.immuni.2018.04.024},
  volume       = {48},
  year         = {2018},
}