The mechanism of repression of the myeloid-specific c-fms gene by Pax5 during B lineage restriction
Hiromi Tagoh,Richard Ingram,Nicola K. Wilson,Giorgia Salvagiotto,Alan J. Warren,Alan J. Warren,Deborah Clarke,Meinrad Busslinger,Constanze Bonifer +8 more
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TLDR
The results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors.Abstract:
The transcription factor Pax5 (BSAP) is required for the expression of a B-cell-specific genetic program and for B-cell differentiation, and also to suppress genes of alternative lineages. The molecular mechanism by which repression of myeloid genes occurs during early B-lineage restriction is unknown and in this study we addressed this question. One of the genes repressed by Pax5 in B cells is the colony-stimulating factor receptor 1 gene (csf1r or c-fms). We examined the changes in chromatin caused by Pax5 activity, and we show that Pax5 is directly recruited to c-fms resulting in the rapid loss of RNA polymerase II binding, followed by loss of transcription factor binding and DNaseI hypersensitivity at all cis-regulatory elements. We also show that Pax5 targets the basal transcription machinery of c-fms by interacting with a binding site within the major transcription start sites. Our results support a model by which Pax5 does not lead to major alterations in chromatin modification, but inhibits transcription by interfering with the action of myeloid transcription factors.read more
Citations
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Pax5: the guardian of B cell identity and function.
TL;DR: Conditional Pax5 inactivation in early and late B lymphocytes revealed an essential role in controlling the identity and function of B cells throughout B lymphopoiesis, and was implicated in human B cell malignancies.
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CSF-1 Receptor Signaling in Myeloid Cells
E. Richard Stanley,Violeta Chitu +1 more
TL;DR: This review describes the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R and describes the mechanism of ligand binding to and activation of the receptor.
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Transcriptional control of granulocyte and monocyte development.
TL;DR: PU.1 directs the hematopoietic stem cell to the lymphoid-myeloid progenitor (LMP) and interacts with GATA-binding protein 1 to inhibit commitment to the megakaryocyte-erythroid progenitors (GMP) stage, while inhibiting lymphoid development via cross-inhibition of Pax5 and potentially other regulators.
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The Transcriptional Regulation of B Cell Lineage Commitment
Stephen L. Nutt,Barbara L. Kee +1 more
TL;DR: This review focuses on recent studies that have revealed that instead of a simple transcriptional hierarchy, efficient B cell commitment and differentiation requires the combinatorial activity of multiple transcription factors in a complex gene regulatory network.
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Regulation of B cell fate commitment and immunoglobulin heavy-chain gene rearrangements by Ikaros.
Damien Reynaud,Ignacio A. Demarco,Karen L. Reddy,Hilde Schjerven,Eric Bertolino,Zhengshan Chen,Stephen T. Smale,Susan Winandy,Harinder Singh,Harinder Singh +9 more
TL;DR: It is shown that the transcription factor EBF restored the generation of CD19+ pro–B cells from Ikaros-deficient hematopoietic progenitors, and is an obligate component of a network that regulates B cell fate commitment and immunoglobulin heavy-chain gene recombination.
References
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Complete block of early B cell differentiation and altered patterning of the posterior midbrain in mice lacking Pax5/BSAP
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Rodney P. DeKoter,Harinder Singh +1 more
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