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Interaction of CNOT3 with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

ABSTRACT: Interaction of CNOT3 with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

PROVIDER: PRJNA345460 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4345330_1.fastq.gz	Fastqsanger.gz
	SRR4345330_2.fastq.gz	Fastqsanger.gz
	SRR4345323_1.fastq.gz	Fastqsanger.gz
	SRR4345323_2.fastq.gz	Fastqsanger.gz
	SRR4345324_1.fastq.gz	Fastqsanger.gz

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Interaction of CNOT3 with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis

Project description:EBF1 interacts with CNOT3 and histidine 240 of EBF1 is a critical residue for this interaction. We studied H240 dependent EBF1 occupancy and gene expression regulation by genome-wide ChIP and microarray analysis. We also performed RNASeq analysis in pro-B cells to study the role of Cnot3 in early B cells development. This SuperSeries is composed of the SubSeries listed below.

2016-11-21 | GSE87637 | GEO

A comprehensive Proteomic Investigation of Ebf1 Heterozygosity in pro-B lymphocytes utilizing Data Independent Acquisition

Project description:Early B cell factor 1 (EBF1) is one of the key transcription factors required for orchestrating B-cell lineage development. Although studies have shown that Ebf1 haploinsufficiency is involved in the development of leukemia, no study has been conducted that characterizes the global effect of Ebf1 heterozygosity on the proteome of pro-B lymphocytes. Here, we employ both DIA (Data Independent Acquisition) and shotgun DDA (Data Dependent Acquisition) workflows for profiling proteins that are differently expressed between Ebf1+/+ and Ebf1+/- cells. Both DDA and DIA were able to reveal the downregulation of the EBF1 transcription factor in Ebf1+/- pro-B lymphocytes. Further examination of differentially expressed proteins by DIA revealed that, similar to EBF1, the expression of other B-cell lineage regulators, such as TCF3 and Pax5, is also down-regulated in Ebf1 heterozygous cells. Functional DIA analysis of differentially expressed proteins showed that EBF1 heterozygosity resulted in the deregulation of at least 8 transcription factors involved in lymphopoiesis, and to the deregulation of key proteins playing crucial roles in survival, development and differentiation of pro-B lymphocytes.

2017-12-20 | PXD008396 | Pride

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1]

Project description:Transcription factor Ebf1 is an important determinant of early B lymphopoiesis. To gain insight into differentiation stage-specific functions of Ebf1, we conditionally inactivated Ebf1. We found that Ebf1 is required for proliferation, survival and signaling of pro-B cells and peripheral B cell subsets. The proliferation defect of Ebf1-deficient pro-B cells, including the impaired expression of IL-7Ra and several cell cycle regulators, is overcome by transformation with v-Abl. The survival defect of transformed Ebf1fl/fl pro-B cells can be rescued by the forced expression of the Ebf1 targets c-Myb or Bcl-xL. In mature B cells, Ebf1 deficiency interferes with the BAFF-R and BCR-dependent Akt signaling pathways, as well as with germinal center formation and class switch recombination. Genome-wide analyses of Ebf1 binding and Ebf1-mediated gene expression in mature B cells and comparison with reported data sets in pro-B cells provide insight into the basis for lineage- and stage-specific functions of Ebf1. EBF1 binding in splenic B cells in mice

2012-04-02 | E-GEOD-35910 | biostudies-arrayexpress

Gene expression profile of Cnot3(+/+) & Cnot3 (∆/∆) pro-B cells

Project description:To study the role Cnot3 in early B cells development, RNASeq analysis of pro-B cells (B220+ and CD43+) was performed in tamoxifen treated Cnot3(fl/fl) RERTCre and Cnot3+/+;RERTCre mice.

2016-11-21 | GSE87635 | GEO

Interaction of CCR4-NOT with EBF1 regulates gene-specific transcription and mRNA stability in B lymphopoiesis.

Project description:Transcription factor EBF1 (early B-cell factor 1) regulates early B-cell differentiation by poising or activating lineage-specific genes and repressing genes associated with alternative cell fates. To identify proteins that regulate the diverse functions of EBF1, we used SILAC (stable isotope labeling by amino acids in cell culture)-based mass spectrometry of proteins associated with endogenous EBF1 in pro-B cells. This analysis identified most components of the multifunctional CCR4-NOT complex, which regulates transcription and mRNA degradation. CNOT3 interacts with EBF1, and we identified histidine 240 in EBF1 as a critical residue for this interaction. Complementation of Ebf1-/- progenitors with EBF1H240A revealed a partial block of pro-B-cell differentiation and altered expression of specific EBF1 target genes that show either reduced transcription or increased mRNA stability. Most deregulated EBF1 target genes show normal occupancy by EBF1H240A, but we also detected genes with altered occupancy, suggesting that the CCR4-NOT complex affects multiple activities of EBF1. Mice with conditional Cnot3 inactivation recapitulate the block of early B-cell differentiation, which we found to be associated with an impaired autoregulation of Ebf1 and reduced expression of pre-B-cell receptor components. Thus, the interaction of the CCR4-NOT complex with EBF1 diversifies the function of EBF1 in a context-dependent manner and may coordinate transcriptional and post-transcriptional gene regulation.

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Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [EBF1]

2012-04-03 | GSE35910 | GEO

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3]

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Functional analysis of CNOT3 in pancreatic beta cells

Project description:Pancreatic β-cells are responsible for production and secretion of insulin in response to increasing blood glucose levels. Therefore, defects in pancreatic β-cell function lead to hyperglycemia and diabetes mellitus. Understanding the molecular mechanisms governing β cell function is crucial for development of novel treatment strategies for this disease. The aim of this project was to investigate the role of Cnot3, part of CCR4-NOT complex, major deadenylase complex in mammals, in pancreatic β cell function. Cnot3βKO islets display decreased expression of key regulators of β cell maturation and function. Moreover, they show an increase of progenitor cell markers, β cell-disallowed genes and genes relevant to altered β cell function. Cnot3βKO islets exhibit altered deadenylation and increased mRNA stability, partly accounting for the increase of those genes. Together, these data reveal that CNOT3-mediated mRNA deadenylation and decay constitute previously unsuspected post-transcriptional mechanisms essential for β cell identity.

2020-08-31 | PXD018403 | Pride

Transcriptome wide analysis of Cnot3 target mRNA in mouse hearts

Project description:Through RNA immunoprecipitation with anti-Cnot3 antiboy from mouse heart lysates and RNA-seq (Cnot3 RIP-seq) and gene ontology analyses, we show the comprehensive picute of cardiac Cnot3 target genes.

2018-08-31 | GSE103629 | GEO

Transcription factor Ebf1 regulates differentiation stage-specific signaling, proliferative expansion and survival of B cells [H3K4me2 and H3K4me3]

2012-04-03 | GSE35914 | GEO