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Pioneering Activity of the C-Terminal Domain of EBF1 Shapes the Chromatin Landscape for B Cell Programming

Boller, Sören
Ramamoorthy, Senthilkumar
Akbas, Duygu
Nechanitzky, Robert
Burger, Lukas
Schübeler, Dirk
Grosschedl, Rudolf
Published in Immunity. 2016, vol. 44, no. 3, p. 527-541
Abstract Lymphopoiesis requires the activation of lineage-specific genes embedded in naive, inaccessible chromatin or in primed, accessible chromatin. The mechanisms responsible for de novo gain of chromatin accessibility, known as "pioneer" function, remain poorly defined. Here, we showed that the EBF1 C-terminal domain (CTD) is required for the regulation of a specific gene set involved in B cell fate decision and differentiation, independently of activation and repression functions. Using genome-wide analysis of DNaseI hypersensitivity and DNA methylation in multipotent Ebf1(-/-) progenitors and derivative EBF1wt- or EBF1ΔC-expressing cells, we found that the CTD promoted chromatin accessibility and DNA demethylation in previously naive chromatin. The CTD allowed EBF1 to bind at inaccessible genomic regions that offer limited co-occupancy by other transcription factors, whereas the CTD was dispensable for EBF1 binding at regions that are occupied by multiple transcription factors. Thus, the CTD enables EBF1 to confer permissive lineage-specific changes in progenitor chromatin landscape.
Keywords AnimalsB-Lymphocytes/physiologyCell Differentiation/geneticsCell Lineage/geneticsCells, CulturedChromatin/metabolismDNA Methylation/geneticsGene Regulatory Networks/geneticsLymphoid Progenitor Cells/physiologyLymphopoiesisMiceMice, KnockoutMice, TransgenicProtein Structure, Tertiary/geneticsTrans-Activators/genetics/metabolism
PMID: 26982363
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Article (Accepted version) (6.7 MB) - public document Free access
Research group Epigénétique et développement (950)
Swiss National Science Foundation: Crosstalk between genetic and epigenetic events in gene expression control and DNA damage response
(ISO format)
BOLLER, Sören et al. Pioneering Activity of the C-Terminal Domain of EBF1 Shapes the Chromatin Landscape for B Cell Programming. In: Immunity, 2016, vol. 44, n° 3, p. 527-541. doi: 10.1016/j.immuni.2016.02.021 https://archive-ouverte.unige.ch/unige:89730

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Deposited on : 2016-12-02

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