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CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

ABSTRACT: CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

PROVIDER: PRJNA530792 | ENA |

REPOSITORIES: ENA

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CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis

Project description:In B lymphopoiesis, activation of the pre-B cell antigen receptor (pre-BCR) is associated with both cell cycle exit and Igk recombination. Yet, how the pre-BCR mediates these functions remains unclear. Herein, we demonstrate that the pre-BCR initiates a feed-forward IRF4-CXC Receptor 4 (CXCR4) amplification loop. ERK activation by CXCR4 then directs the development of small and immature B cells including orchestrating cell cycle exit, pre-BCR repression, Igk recombination and BCR expression. In contrast, escape from IL-7 and pre-BCR expression have only modest effects on B cell developmental transcriptional and epigenetic programs. These data demonstrate a direct and central role for CXCR4 in orchestrating late B cell lymphopoiesis. Furthermore, in the context of previous findings, our data provide a three-receptor system sufficient to recapitulate the essential features of B lymphopoiesis in vitro.

2019-06-18 | GSE129311 | GEO

CXCR4 signaling directs Igk recombination and the molecular mechanisms of late B lymphopoiesis.

Project description: Not available

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BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis

Project description:Transcription factor (TF) networks determine cell fate in hematopoiesis. However, how TFs cooperate with other regulatory mechanisms to instruct transcription remains poorly understood. We demonstrate in small pre-B cells, that the lineage restricted epigenetic reader BRWD1 closes early development enhancers and opens the enhancers of late B lymphopoiesis to TF binding. BRWD1 differentially regulated over 7000 genes including repressing proliferative and inducing differentiation programs. However, BRWD1 did not regulate expression of transcription factors required for B lymphopoiesis. Hypogammaglobulinemia patients with BRWD1 mutations had B cell transcriptional profiles and enhancer landscapes similar to those observed in Brwd1-/- mice. These data indicate that in both mice and humans, BRWD1 is a master orchestrator of enhancer accessibility that cooperates with TF networks to drive late B cell development.

2018-08-11 | GSE103057 | GEO

BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis

Project description:BRWD1 orchestrates epigenetic landscape of late B lymphopoiesis

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RecG Directs DNA Synthesis During Double-Strand Break Repair [ChIP-seq]

Project description:In the bacterium Escherichia coli, RecG directs DNA synthesis during the repair of DNA double-strand breaks by homologous recombination.

2016-05-19 | GSE77181 | GEO

Gene expression pattern in CXCR4+ and CXCR4- subpopulation of breast cancer cells

Project description:The goal of this study was to identify signalling molecules downstream of CXCR4 in breast cancer cells. For this purpose, we sorted CXCR4-positive and CXCR4-negative cells from MDA-MB-231 breast cancer cell line by flow cytometry and performed microarrays analysis. Three sets of samples, each in quadruplicate, were analyzed. These include CXCR4-positive subpopulation, CXCR4-positive subpopulation treated with SDF-1 (ligand for CXCR4, also called CXCL12) for one hour and CXCR4-negative subpopulation.

2010-04-28 | E-GEOD-15893 | biostudies-arrayexpress

RecG Directs DNA Synthesis During Double-Strand Break Repair [Chromosomal marker frequency analysis]

Project description:In the bacterium Escherichia coli, RecG directs DNA synthesis during the repair of DNA double-strand breaks by homologous recombination.

2016-05-19 | GSE77183 | GEO

RecG Directs DNA Synthesis During Double-Strand Break Repair [ChIP-seq]

Project description:In the bacterium Escherichia coli, RecG directs DNA synthesis during the repair of DNA double-strand breaks by homologous recombination. Examination of RecA binding during double-strand break repair in Escherichia coli in the presence and absence of RecG protein

2016-05-19 | E-GEOD-77181 | biostudies-arrayexpress

The B cell identity factor Pax5 regulates distinct transcriptional programs in early and late B lymphopoiesis

Project description:Pax5 controls the identity and development of B cells by repressing lineage-inappropriate genes and activating B-cell-specific genes. Here, we used genome-wide approaches to identify Pax5 target genes in pro-B and mature B cells. In these cell types, Pax5 bound to 40% of the cis- regulatory elements defined by mapping Dnase I hypersensitive (DHS) sites, transcription start sites and histone modifications. Although Pax5 bound to 8,000 target genes, it regulated only 4% of them in pro-B and mature B cells by inducing enhancers at activated genes and eliminating DHS sites at repressed genes. Pax5-regulated genes in pro-B cells account for 23% of all expression changes occurring between common lymphoid progenitors and committed pro-B cells, which identifies Pax5 as an important regulator of this developmental transition. Regulated Pax5 target genes minimally overlap in pro-B and mature B cells, which reflects massive expression changes between these cell types. Hence, Pax5 controls B cell identity and function by regulating distinct target genes in early and late B lymphopoiesis. 44 samples (16 RNA-seq, 15 ChIP-seq, 6 DHS-seq, 5 Bio-ChIP-seq, 2 CAGE-seq). All but four samples in in 2 biological replicates (8819, 8275, 8095, 8666). WT and experimental samples are provided.

2012-06-14 | E-GEOD-38046 | biostudies-arrayexpress

RecG Directs DNA Synthesis During Double-Strand Break Repair [Chromosomal marker frequency analysis]

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2016-05-19 | E-GEOD-77183 | biostudies-arrayexpress

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