Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening

Alexandre Mayran, Kevin Sochodolsky, Konstantin Khetchoumian, Juliette Harris, Yves Gauthier, Amandine Bemmo, Aurelio Balsalobre and Jacques Drouin ()
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Alexandre Mayran: Institut de Recherches Cliniques de Montréal (IRCM)
Kevin Sochodolsky: Institut de Recherches Cliniques de Montréal (IRCM)
Konstantin Khetchoumian: Institut de Recherches Cliniques de Montréal (IRCM)
Juliette Harris: Institut de Recherches Cliniques de Montréal (IRCM)
Yves Gauthier: Institut de Recherches Cliniques de Montréal (IRCM)
Amandine Bemmo: Institut de Recherches Cliniques de Montréal (IRCM)
Aurelio Balsalobre: Institut de Recherches Cliniques de Montréal (IRCM)
Jacques Drouin: Institut de Recherches Cliniques de Montréal (IRCM)

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-11791-9

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