Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening

Nat Commun. 2019 Aug 23;10(1):3807. doi: 10.1038/s41467-019-11791-9.


Pioneer transcription factors are characterized by having the unique property of enabling the opening of closed chromatin sites, for implementation of cell fates. We previously found that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire, which allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigate the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatin landscapes are defined by scRNAseq and chromatin accessibility profiling. We find that in vivo deployment of the melanotrope enhancer repertoire and chromatin opening requires both Pax7 and Tpit. In cells, binding of heterochromatin targets by Pax7 is independent of Tpit but Pax7-dependent chromatin opening requires Tpit. The present work shows that pioneer core properties are limited to the ability to recognize heterochromatin targets and facilitate nonpioneer binding. Chromatin opening per se may be provided through cooperation with nonpioneer factors.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Differentiation / genetics*
  • Cell Line, Tumor
  • Corticotrophs / physiology
  • Enhancer Elements, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Heterochromatin / metabolism*
  • Homeodomain Proteins / genetics
  • Homeodomain Proteins / metabolism*
  • Male
  • Melanotrophs / physiology
  • Mice, Knockout
  • PAX7 Transcription Factor / genetics
  • PAX7 Transcription Factor / metabolism*
  • Protein Binding / genetics
  • Sequence Analysis, RNA
  • Single-Cell Analysis
  • T-Box Domain Proteins / genetics
  • T-Box Domain Proteins / metabolism*


  • Heterochromatin
  • Homeodomain Proteins
  • PAX7 Transcription Factor
  • Pax7 protein, mouse
  • T-Box Domain Proteins
  • Tbx19 protein, mouse