Essential control of early B-cell development by Mef2 transcription factors
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
SUBMITTER: Julia Herglotz
PROVIDER: E-GEOD-73563 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. RNA-seq experiments were performed from Klf2 overexpressing BMiFLT3 (15-3) cells to identify genes regulated by Klf2
2015-12-14 | E-GEOD-73559 | biostudies-arrayexpress
Project description:The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. RNA-seq experiments were performed from Klf2 knockout proB-cells versus control cells to identify genes regulated by Klf2
2015-12-14 | E-GEOD-73560 | biostudies-arrayexpress
Project description:The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. RNA-seq experiments were performed from Mef2c/d knockout proB-cells versus control cells to identify genes regulated by Klf2
2015-12-14 | E-GEOD-73561 | biostudies-arrayexpress
Project description:The sequential activation of distinct developmental gene networks governs the ultimate identity of a cell, but the mechanisms by which downstream programs are activated are incompletely understood. The preB-cell receptor (preBCR) is an important checkpoint of B-cell development and essential for a preB-cell to traverse into an immature B-cell. Here, we show that activation of Mef2 transcription factors by preBCR is necessary for initiating the subsequent genetic network. We demonstrate that B-cell development is blocked at the preB-cell stage in mice deficient for Mef2c and Mef2d transcription factors and that preBCR signaling enhances the transcriptional activity of Mef2c/d through phosphorylation by the ERK5 mitogen activating kinase. This activation is instrumental in inducing Krüppel-like factor 2 and several immediate early genes of the AP1 and Egr family. Finally, we show that Mef2 proteins cooperate with the products of their target genes (Irf4 and Egr2) to induce secondary waves of transcriptional regulation. Our findings uncover a novel role for Mef2c/d in coordinating the transcriptional network that promotes early B-cell development. RNA-seq experiments were performed from Blnk-/- preB-cells with an integration of BLNK-ERt2 to identify genes regulated after preBCR signaling
2015-12-14 | E-GEOD-73562 | biostudies-arrayexpress
Project description:We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations. GMP and MEP were isolated from Runx1+/+-Tg(vav-Cre) and Runx1fl/fl-Tg(vav-Cre) mice as well as Runx1fl/fl-Tg(vav-Cre) XMP, total RNA extracted and sequenced
2016-07-01 | E-GEOD-81181 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-01 | E-GEOD-81182 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2016-07-25 | E-GEOD-75508 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2015-12-07 | E-GEOD-59005 | biostudies-arrayexpress
Project description:We sequenced total RNA from Dirofilaria immitis in order to generate the first tissue-specific gene expression profile of a filarial nematode and its Wolbachia endosymbiont. Examination of transcript levels in 7 different Dirofilaria immitis tissues, in duplicate, using Illumina GAIIx.
2016-06-01 | E-GEOD-67894 | biostudies-arrayexpress
Project description:We adapted the yeast clogger system to Drosophila motoneurons to block TOM-TIM23-mediated import with temporal control. Sustained import stress converts somatic mitochondria into donut-shaped structures, depletes functional mitochondria from synaptic terminals, and causes progressive neurodegeneration with impaired neurotransmitter release and locomotor dysfunction. This neurodegeneration is mechanistically distinct from mitochondrial absence, as miro mutant neurons that completely lack presynaptic mitochondria do not degenerate. This dataset includes RNA-seq reads from an experiment when mito-IMMDHFR expression was induced pan-neuronally using the TARGET system (n-syb-Gal4; tub-Gal80ts) by shifting animals from 18°C to 29°C for 1, 2, or 3 days prior to collection at the wandering third instar larval stage.
2026-06-18 | E-MTAB-17059 | biostudies-arrayexpress