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| Home > Publications database > Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming. |
| Home > Publications database > Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B-cell programming. |
| Journal Article | DKFZ-2018-00236 |
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2018
HighWire Press
Stanford, Calif.
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Please use a persistent id in citations: doi:10.1101/gad.309583.117
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 arrestedEbf1-/-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 forCd79apromoter 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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