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

Autor: Rudolf Grosschedl, Duygu Akbas, Dirk Schübeler, Robert Nechanitzky, Rabih Murr, Senthilkumar Ramamoorthy, Sören Boller, Lukas Burger
Rok vydání: 2016
Předmět:
0301 basic medicine
Histone-modifying enzymes
Cell Differentiation/genetics
Immunology
Trans-Activators/genetics/metabolism
Mice
Transgenic
Biology
Chromatin remodeling
Chromatin/metabolism
Protein Structure
Tertiary/genetics
03 medical and health sciences
Mice
Cell Lineage/genetics
Animals
Immunology and Allergy
ddc:576.5
Cell Lineage
Gene Regulatory Networks
Transcription factor
ChIA-PET
Cells
Cultured
Genetics
Mice
Knockout
B-Lymphocytes
B-Lymphocytes/physiology
Lymphopoiesis
Pioneer factor
Cell Differentiation
DNA Methylation
Lymphoid Progenitor Cells
Lymphoid Progenitor Cells/physiology
Chromatin
Cell biology
Protein Structure
Tertiary
030104 developmental biology
DNA demethylation
Infectious Diseases
DNA methylation
Trans-Activators
DNA Methylation/genetics
Gene Regulatory Networks/genetics
Zdroj: Immunity
Immunity, Vol. 44, No 3 (2016) pp. 527-541
ISSN: 1074-7613
DOI: 10.1016/j.immuni.2016.02.021
Popis: 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.
Databáze: OpenAIRE
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