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  A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin

Wang, Y., Zolotarev, N., Yang, C.-Y., Rambold, A., Mittler, G., & Grosschedl, R. (2020). A Prion-like Domain in Transcription Factor EBF1 Promotes Phase Separation and Enables B Cell Programming of Progenitor Chromatin. Immunity, 53, 1151-1167. doi:10.1016/j.immuni.2020.10.009.

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Wang 2020_Immunity.pdf (Publisher version), 5MB
 
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 Creators:
Wang, Yuanting1, Author
Zolotarev, Nikolay1, Author
Yang, Cheng-Yuan1, Author
Rambold, Angelika2, Author              
Mittler, Gerhard2, Author              
Grosschedl, Rudolf1, Author              
Affiliations:
1Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243650              

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Free keywords: Brg1; EBF1; EWSR1; FUS; chromatin; phase separation; pioneer transcription factor
 Abstract: Establishment of B-lineage-specific gene expression requires the binding of transcription factors to inaccessible chromatin of progenitors. The transcription factor EBF1 can bind genomic regions prior to the detection of chromatin accessibility in a manner dependent on EBF1's C-terminal domain (CTD) and independent of cooperating transcription factors. Here, we studied the mechanism whereby the CTD enables this pioneering function. The CTD of EBF1 was dispensable for initial chromatin targeting but stabilized occupancy via recruitment of the chromatin remodeler Brg1. We found that the CTD harbors a prion-like domain (PLD) with an ability of liquid-liquid phase separation, which was enhanced by interaction of EBF1 with the RNA-binding protein FUS. Brg1 also partitioned into phase-separated FUS condensates and coincided with EBF1 and FUS foci in pro-B cells. Heterologous PLDs conferred pioneering function on EBF1ΔCTD. Thus, the phase separation ability of EBF1 facilitates Brg1-mediated chromatin opening and the transition of naive progenitor chromatin to B-lineage-committed chromatin.

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Language(s): eng - English
 Dates: 2020-12-15
 Publication Status: Published online
 Pages: -
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 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.immuni.2020.10.009
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Title: Immunity
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 53 Sequence Number: - Start / End Page: 1151 - 1167 Identifier: ISSN: 1074-7613
CoNE: https://pure.mpg.de/cone/journals/resource/954925604783