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

Jan 25, 2019

Received Date: 15th January 19

Pioneer transcription factors are coined as having the unique property of “opening closed chromatin sites” for implementation of cell fates. We previously showed that the pioneer Pax7 specifies melanotrope cells through deployment of an enhancer repertoire: this allows binding of Tpit, a nonpioneer factor that determines the related lineages of melanotropes and corticotropes. Here, we investigated the relation between these two factors in the pioneer mechanism. Cell-specific gene expression and chromatin landscapes were defined by scRNAseq and chromatin accessibility profiling. We found 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.

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This is an abstract of a preprint hosted on an independent third party site. It has not been peer reviewed but is currently under consideration at Nature Communications.

Nature Communications

Nature Research, Springer Nature