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  Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming

Li, R., Cauchy, P., Ramamoorthy, S., Boller, S., Chevez, L., & Grosschedl, R. (2018). Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming. Genes and Development, 32, 96-111. doi:10.1101/gad.309583.117.

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Item Permalink: http://hdl.handle.net/21.11116/0000-0002-7185-8 Version Permalink: http://hdl.handle.net/21.11116/0000-0005-C840-1
Genre: Journal Article

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Li et al..pdf (Publisher version), 12MB
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https://www.pnas.org/content/115/20/5253.long (Publisher version)
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 Creators:
Li , Rui1, Author
Cauchy, Pierre1, Author              
Ramamoorthy, Senthilkumar1, Author
Boller, Sören1, Author
Chevez, Lukas2, Author
Grosschedl, Rudolf1, Author              
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, 79108 Freiburg, DE, ou_2243640              
2External Organizations, ou_persistent22              

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Free keywords: EPF1, Pax5, IRF4, B-cell programming, chromatin, DNA methylation
 Abstract: B-cell fate determination requires the action of transcription factors that operate in a regulatory network to activate B-lineage genes and repress lineage-inappropriate genes. However, the dynamics and hierarchy of events in B-cell programming remain obscure. To uncouple the dynamics of transcription factor expression from functional consequences, we generated induction systems in developmentally arrested Ebf1-/- pre-pro-B cells to allow precise experimental control of EBF1 expression in the genomic context of progenitor cells. Consistent with the described role of EBF1 as a pioneer transcription factor, we show in a time-resolved analysis that EBF1 occupancy coincides with EBF1 expression and precedes the formation of chromatin accessibility. We observed dynamic patterns of EBF1 target gene expression and sequential up-regulation of transcription factors that expand the regulatory network at the pro-B-cell stage. A continuous EBF1 function was found to be required for Cd79a promoter activity and for the maintenance of an accessible chromatin domain that is permissive for binding of other transcription factors. Notably, transient EBF1 occupancy was detected at lineage-inappropriate genes prior to their silencing in pro-B cells. Thus, persistent and transient functions of EBF1 allow for an ordered sequence of epigenetic and transcriptional events in B-cell programming.

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Language(s): eng - English
 Dates: 2018-01-15
 Publication Status: Published in print
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 Rev. Type: Peer
 Identifiers: DOI: 10.1101/gad.309583.117
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Title: Genes and Development
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 32 Sequence Number: - Start / End Page: 96 - 111 Identifier: ISSN: 0890-9369
CoNE: https://pure.mpg.de/cone/journals/resource/954925557453