Mechanisms governing the pioneering and redistribution capabilities of the non-classical pioneer PU.1

Julia Minderjahn, Andreas Schmidt, Andreas Fuchs, Rudolf Schill, Johanna Raithel, Magda Babina, Christian Schmidl, Claudia Gebhard, Sandra Schmidhofer, Karina Mendes, Anna Ratermann, Dagmar Glatz, Margit Nützel, Matthias Edinger, Petra Hoffman, Rainer Spang, Gernot Längst, Axel Imhof, Michael Rehli*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

26 Citations (Scopus)

Abstract

Establishing gene regulatory networks during differentiation or reprogramming requires master or pioneer transcription factors (TFs) such as PU.1, a prototype master TF of hematopoietic lineage differentiation. To systematically determine molecular features that control its activity, here we analyze DNA-binding in vitro and genome-wide in vivo across different cell types with native or ectopic PU.1 expression. Although PU.1, in contrast to classical pioneer factors, is unable to access nucleosomal target sites in vitro, ectopic induction of PU.1 leads to the extensive remodeling of chromatin and redistribution of partner TFs. De novo chromatin access, stable binding, and redistribution of partner TFs both require PU.1’s N-terminal acidic activation domain and its ability to recruit SWI/SNF remodeling complexes, suggesting that the latter may collect and distribute co-associated TFs in conjunction with the non-classical pioneer TF PU.1.
Original languageEnglish
Article number402
JournalNature Communications
Volume11
Issue number1
DOIs
Publication statusPublished - 1 Dec 2020
Externally publishedYes

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