HOX paralogs selectively convert binding of ubiquitous transcription factors into tissue-specific patterns of enhancer activation

Research output: Contribution to journalArticlepeer-review

  • External authors:
  • Laure Bridoux
  • Peyman Zarrineh
  • Joshua Mallen
  • Victor Latorre
  • Frank Ladam
  • Marta Losa
  • Charles Sagerstrom

Abstract

Gene expression programs determine cell fate in embryonic development and their dysregulation results in disease. Transcription factors (TFs) control gene expression by binding to enhancers, but how TFs select and activate their target enhancers is still unclear. HOX TFs share conserved homeodomains with highly similar sequence recognition properties, yet they impart the identity of different animal body parts. To understand how HOX TFs control their specific transcriptional programs in vivo, we compared HOXA2 and HOXA3 binding profiles in the mouse embryo. HOXA2 and HOXA3 directly cooperate with TALE TFs and selectively target different subsets of a broad TALE chromatin platform. Binding of HOX and tissue-specific TFs convert low affinity TALE binding into high confidence, tissue-specific binding events, which bear the mark of active enhancers. We propose that HOX paralogs, alone and in combination with tissue-specific TFs, generate tissue-specific transcriptional outputs by modulating the activity of TALE TFs at selected enhancers.

Bibliographical metadata

Original languageEnglish
Article numbere1009162
Pages (from-to)e1009162
JournalPLoS Genetics
Volume16
Issue number12
DOIs
Publication statusPublished - 14 Dec 2020