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

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE107242 | GEO | 2018/02/20

REPOSITORIES: GEO

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

Project description: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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Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B cell programming [EBF1-ChIP-Seq-Cre]

Project description:EBF1 is essential for B cell specification and commitment. To explore the dynamics of EBF1 initiated B cell programming, we performed EBF1 ChIP-seq, ATAC-seq, bisulfite-seq, RNA-seq and several histone ChIP-seq analyses at different stages of the transition from Ebf1-/- pre-pro-B to pro-B triggered by EBF1 restoration. We also performed Pax5 ChIP-seq in Ebf1-/- pre-pro-B cell and EBF1-restored pro-B cell to study the pioneering function of EBF1 that allows other transcription factors to access certain chromatin sites.

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Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B cell programming [EBF1-ChIP-Seq-Tet-On]

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Dynamic EBF1 occupancy directs sequential epigenetic and transcriptional events in B cell programming [Bisulfite-Seq-Cre]

2018-02-20 | GSE107241 | GEO