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Publication : Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening.

First Author  Mayran A Year  2019
Journal  Nat Commun Volume  10
Issue  1 Pages  3807
PubMed ID  31444346 Mgi Jnum  J:279408
Mgi Id  MGI:6362366 Doi  10.1038/s41467-019-11791-9
Citation  Mayran A, et al. (2019) Pioneer and nonpioneer factor cooperation drives lineage specific chromatin opening. Nat Commun 10(1):3807
abstractText  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.
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