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Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.

Publication ,  Journal Article
Li, T; Liu, Q; Chen, Z; Fang, K; Huang, F; Fu, X; Wang, Q; Jin, VX
Published in: Nat Commun
June 7, 2022

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.

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 7, 2022

Volume

13

Issue

1

Start / End Page

3145

Location

England

Related Subject Headings

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

Citation

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Li, T., Liu, Q., Chen, Z., Fang, K., Huang, F., Fu, X., … Jin, V. X. (2022). Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model. Nat Commun, 13(1), 3145. https://doi.org/10.1038/s41467-022-30960-x
Li, Tianbao, Qi Liu, Zhong Chen, Kun Fang, Furong Huang, Xueqi Fu, Qianben Wang, and Victor X. Jin. “Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.Nat Commun 13, no. 1 (June 7, 2022): 3145. https://doi.org/10.1038/s41467-022-30960-x.
Li T, Liu Q, Chen Z, Fang K, Huang F, Fu X, et al. Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model. Nat Commun. 2022 Jun 7;13(1):3145.
Li, Tianbao, et al. “Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model.Nat Commun, vol. 13, no. 1, June 2022, p. 3145. Pubmed, doi:10.1038/s41467-022-30960-x.
Li T, Liu Q, Chen Z, Fang K, Huang F, Fu X, Wang Q, Jin VX. Dynamic nucleosome landscape elicits a noncanonical GATA2 pioneer model. Nat Commun. 2022 Jun 7;13(1):3145.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

June 7, 2022

Volume

13

Issue

1

Start / End Page

3145

Location

England

Related Subject Headings

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