RT Journal Article
SR Electronic
T1 Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 472647
DO 10.1101/472647
A1 Alexandre Mayran
A1 Kevin Sochodolsky
A1 Konstantin Khetchoumian
A1 Juliette Harris
A1 Yves Gauthier
A1 Amandine Bemmo
A1 Aurelio Balsalobre
A1 Jacques Drouin
YR 2019
UL http://biorxiv.org/content/early/2019/01/22/472647.abstract
AB 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.