Mus musculus
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA167176 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR499674.fastq.gz | Fastqsanger.gz | |||
| SRR499675.fastq.gz | Fastqsanger.gz | |||
| SRR499676.fastq.gz | Fastqsanger.gz | |||
| SRR499677.fastq.gz | Fastqsanger.gz | |||
| SRR499678.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 83 |
Similar Datasets
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
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.
2012-06-14 | GSE38046 | GEO
Project description:B lymphopoiesis is a key developmental event orchestrated by a complex combinatorial action of lineage-specific transcription factors. In early B cell progenitors, lineage commitment is directly mediated by the master regulator PAX5, whose deficiency is commonly associated with B cell Acute Lymphoblastic Leukemia (B-ALL). Despite its essential role in mammalian immunity, the regulatory mechanisms that control PAX5 function remain largely unknown. Here we show that NAD+-dependent enzyme SIRT7 coordinates B cell development progression through PAX5. We have identified a SIRT7-dependent regulatory switch based on dynamic deacetylation of a single PAX5 residue, which controls its activity and thereby B cell fate. While a PAX5K198 acetylated mimic is incapable of inducing both B cell development and identity due to reduced protein stability and impaired binding to chromatin, deacetylation of this residue boosts PAX5 activity, leading to massive gene repression and in vivo restoration of B cell commitment but not differentiation. These findings suggest an unexpected uncoupling of hematopoietic differentiation and lineage commitment. Further supporting the functional relevance of the SIRT7-PAX5 axis, the interplay between both factors is conserved in human B-ALL, where high SIRT7 expression is an independent good prognostic factor. Our findings unveil a crucial mechanism in the regulation of B cell production based on the control of PAX5 function and underscore the key role of Sirtuins in the regulation of the immune system.
2024-09-20 | PXD046457 | Pride
Project description:Early B-lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. Here, we used acute protein degradation in vivo to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B-cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and maintain cell viability in vivo by activating Bcl2l1. Ikaros and Aiolos cooperatively control early B-cell development and act as dedicated repressors to suppress open chromatin at their target genes. The surrogate light-chain genes Igll1 and Vpreb1 are directly activated by Ebf1 and Pax5 in pro-B cells and directly repressed by Ikaros and Aiolos in small pre-B cells. Pax5 and E2A contribute to V(D)J recombination by activating Rag1, Rag2, Dntt, Irf4 and Irf8. Like Pax5, Ebf1 also represses the cohesin-release factor gene Wapl to mediate prolonged loop extrusion across the Igh locus. In summary, in vivo protein degradation has provided unprecedented insight into the control of early B-lymphopoiesis by five transcription factors.
2024-06-21 | GSE259355 | GEO
Project description:Early B-lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. Here, we used acute protein degradation in vivo to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B-cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and maintain cell viability in vivo by activating Bcl2l1. Ikaros and Aiolos cooperatively control early B-cell development and act as dedicated repressors to suppress open chromatin at their target genes. The surrogate light-chain genes Igll1 and Vpreb1 are directly activated by Ebf1 and Pax5 in pro-B cells and directly repressed by Ikaros and Aiolos in small pre-B cells. Pax5 and E2A contribute to V(D)J recombination by activating Rag1, Rag2, Dntt, Irf4 and Irf8. Like Pax5, Ebf1 also represses the cohesin-release factor gene Wapl to mediate prolonged loop extrusion across the Igh locus. In summary, in vivo protein degradation has provided unprecedented insight into the control of early B-lymphopoiesis by five transcription factors.
2024-06-21 | GSE260522 | GEO
Project description:Early B-lymphopoiesis depends on E2A, Ebf1, Pax5 and Ikaros family members. Here, we used acute protein degradation in vivo to identify direct target genes of these transcription factors in pro-B, small pre-B and immature B-cells. E2A, Ebf1 and Pax5 predominantly function as transcriptional activators by inducing open chromatin at their target genes, have largely unique functions and maintain cell viability in vivo by activating Bcl2l1. Ikaros and Aiolos cooperatively control early B-cell development and act as dedicated repressors to suppress open chromatin at their target genes. The surrogate light-chain genes Igll1 and Vpreb1 are directly activated by Ebf1 and Pax5 in pro-B cells and directly repressed by Ikaros and Aiolos in small pre-B cells. Pax5 and E2A contribute to V(D)J recombination by activating Rag1, Rag2, Dntt, Irf4 and Irf8. Like Pax5, Ebf1 also represses the cohesin-release factor gene Wapl to mediate prolonged loop extrusion across the Igh locus. In summary, in vivo protein degradation has provided unprecedented insight into the control of early B-lymphopoiesis by five transcription factors.
2024-06-21 | GSE259358 | GEO
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
Project description:The transcription factor Pax5 is essential for B cell commitment in the mouse, where it represses lineage-inappropriate gene expression, while simultaneously activating the B cell gene expression program. We have performed a global gene expression screen of wild type and Pax5-deficient pro-B cells in an attempt to identify the crucial Pax5 targets in early B-lymphopoiesis. We have also included Rag1-/- and wild type (+/+) proB cells starved of the cytokine IL-7 for 4 hours as controls. Rag1-/- proB cells are incapable of further differentiation due to an absence of immunoglobulin recombination and IL-7 is the major cytokine regulating proB cell growth. Keywords: comparison of genetically modified cell-lines
2007-10-26 | GSE9345 | GEO
Project description:B lymphopoiesis is a key developmental event orchestrated by a complex combinatorial action of lineage-specific transcription factors. In early B cell progenitors, lineage commitment is directly mediated by the master regulator Pax5, whose deficiency is commonly associated with B cell Acute Lymphoblastic Leukemia (B-ALL). Despite its essential role in mammalian immunity, the regulatory mechanisms that control Pax5 function remain largely unknown. Here we show that NAD+-dependent enzyme SIRT7 coordinates B cell development progression through regulation of Pax5 function. We have identified a SIRT7-dependent regulatory switch based on dynamic deacetylation of a single Pax5 residue, which controls its activity and thereby B cell fate. While a PAX5K198 acetylated mimic is incapable of inducing both B cell development and identity due to reduced protein stability and impaired binding to chromatin, deacetylation of this residue boosts Pax5 activity, leading to massive gene repression and restoration of B cell commitment but not differentiation in vivo. These findings suggest an unexpected uncoupling of hematopoietic differentiation and lineage commitment. Further supporting the functional relevance of the SIRT7-PAX5 axis, the interplay between both factors is largely conserved in human B-ALL, where high SIRT7 expression is an independent good prognostic factor. Our findings unveil a crucial mechanism in the regulation of B-cell production based on the control of Pax5 function and underscore the key role of Sirtuins in the regulation of the immune system.
2024-09-19 | GSE246370 | GEO
Project description:STAT5 and IL-7 signaling are thought to control B-lymphopoiesis by regulating key transcription factor genes and activating VH gene segments at the Igh locus. Using conditional mutagenesis, we demonstrate that transgenic Bcl2 expression rescued the development of Stat5-deleted pro-B cells by compensating for the loss of Mcl-1. Ebf1 and Pax5 expression as well as VH recombination were normal in Bcl2-rescued pro-B cells lacking STAT5 or IL-7Ra. In agreement with this finding, STAT5-expressing pro-B cells contained little or no active chromatin at most VH genes. In contrast, Igk rearrangements were increased in STAT5- or IL-7Ra-deficient pro-B cells, consistent with direct binding of STAT5 to the intronic iEk enhancer in wild-type pro-B cells. Hence, STAT5 and IL-7 signaling control cell survival and suppress premature Igk recombination in early B-lymphopoiesis. comparison of wt vs Rag2-/- pro-B cells
2010-07-28 | E-GEOD-18278 | biostudies-arrayexpress