title: The regulatory network of B-cell differentiation: a focused view of early B-cell factor 1 function.
abstract: During the last decades, many studies have investigated the transcriptional and epigenetic regulation of lineage decision in the hematopoietic system. These efforts led to a model in which extrinsic signals and intrinsic cues establish a permissive chromatin context upon which a regulatory network of transcription factors and epigenetic modifiers act to guide the differentiation of hematopoietic lineages. These networks include lineage-specific factors that further modify the epigenetic landscape and promote the generation of specific cell types. The process of B lymphopoiesis requires a set of transcription factors, including Ikaros, PU.1, E2A, and FoxO1 to 'prime' cis-regulatory regions for subsequent activation by the B-lineage-specific transcription factors EBF1 and Pax-5. The expression of EBF1 is initiated by the combined action of E2A and FoxO1, and it is further enhanced and maintained by several positive feedback loops that include Pax-5 and IL-7 signaling. EBF1 acts in concert with Ikaros, PU.1, Runx1, E2A, FoxO1, and Pax-5 to establish the B cell-specific transcription profile. EBF1 and Pax-5 also collaborate to repress alternative cell fates and lock cells into the B-lineage fate. In addition to the functions of EBF1 in establishing and maintaining B-cell identity, EBF1 is required to coordinate differentiation with cell proliferation and survival.
authors.affiliation: Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Freiburg, Germany.
authors.forename: Sören
authors.initials: S
authors.lastname: Boller
authors.forename: Rudolf
authors.initials: R
authors.lastname: Grosschedl
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D019070:Cell Lineage; D049109:Cell Proliferation; D002470:Cell Survival; D044127:Epigenesis, Genetic; D025461:Feedback, Physiological; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks / Q000276:immunology; D042421:Histone Code / Q000502:physiology*; D006706:Homeostasis; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism; D038041:Lymphopoiesis; D015534:Trans-Activators / Q000378:metabolism*
chemical_list: C081976:EBF1 protein, human; D015851:Interleukin-7; D015534:Trans-Activators
keywords: B-cell commitment; B-cell differentiation; EBF1; lineage specification; regulatory network