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Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model. Nat Commun 2022 Jun 07;13(1):3145

Date

06/08/2022

Pubmed ID

35672415

Pubmed Central ID

PMC9174260

DOI

10.1038/s41467-022-30960-x

Scopus ID

2-s2.0-85131472527 (requires institutional sign-in at Scopus site)   2 Citations

Abstract

Knowledge gaps remain on how nucleosome organization and dynamic reorganization are governed by specific pioneer factors in a genome-wide manner. In this study, we generate over three billons of multi-omics sequencing data to exploit dynamic nucleosome landscape governed by pioneer factors (PFs), FOXA1 and GATA2. We quantitatively define nine functional nucleosome states each with specific characteristic nucleosome footprints in LNCaP prostate cancer cells. Interestingly, we observe dynamic switches among nucleosome states upon androgen stimulation, accompanied by distinct differential (gained or lost) binding of FOXA1, GATA2, H1 as well as many other coregulators. Intriguingly, we reveal a noncanonical pioneer model of GATA2 that it initially functions as a PF binding at the edge of a nucleosome in an inaccessible crowding array. Upon androgen stimulation, GATA2 re-configures an inaccessible to accessible nucleosome state and subsequently acts as a master transcription factor either directly or recruits signaling specific transcription factors to enhance WNT signaling in an androgen receptor (AR)-independent manner. Our data elicit a pioneer and master dual role of GATA2 in mediating nucleosome dynamics and enhancing downstream signaling pathways. Our work offers structural and mechanistic insight into the dynamics of pioneer factors governing nucleosome reorganization.

Author List

Li T, Liu Q, Chen Z, Fang K, Huang F, Fu X, Wang Q, Jin VX

Author

Victor X. Jin PhD Professor in the Institute for Health and Equity department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Androgens
GATA2 Transcription Factor
Humans
Male
Nucleosomes
Prostate
Prostatic Neoplasms
Receptors, Androgen
Signal Transduction