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Pol II pausing is a milestone on the road to complex animals

ABSTRACT: PRO-seq experiments in multiple organisms. Also, PRO-seq experiment of Nelfb and Nelfe degron mESC in serum/LIF with or without dTAG-13.

ORGANISM(S): Perkinsus marinus Escherichia coli Nematostella vectensis Mus musculus Daphnia pulex Strongylocentrotus purpuratus Haloferax mediterranei Creolimax fragrantissima Dryas iulia Capsaspora owczarzaki Sphaeroforma arctica Dictyostelium discoideum

PROVIDER: GSE223913 | GEO | 2024/02/05

REPOSITORIES: GEO

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RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription

Project description:PRO-seq experiment of Nelfb deg mESC in serum/LIF or during pluripotency transitions, with or without dTAG-13.

2022-02-16 | GSE196653 | GEO

RNA Pol II pausing facilitates phased pluripotency transitions by buffering transcription

Project description:ChIP-seq experiments of NELFB (HA), NELFE, and Spt5 in mESCs under serum/LIF conditions. The experiments where performed with and without dTAG degradation of NELFB

2022-02-28 | GSE196543 | GEO

Rapid and efficient adaptation of the dTAG system in mammalian development reveals stage specific requirements of NELF

Project description:mRNA expression profile of late 2-cell mouse embryos cultured +/- dTAG-13 to degrade NELFB from the zygote stage.

2022-02-19 | GSE185099 | GEO

Essential Signaling Function of Cytoplasmic NELFB Independent of RNA Polymerase II Pausing

Project description:Biochemical studies have established that the four-subunit negative elongation factor (NELF) complex mediates RNA polymerase II (Pol II) pausing at promoter proximal regions. Genetic ablation of individual NELF subunits destabilizes the entire NELF complex and causes lethality of cultured cells, leading to the prevailing concept that NELF-mediated Pol II pausing is essential for cell survival. Using separation-of-function mutations, we show here that NELFB’s effects on cell proliferation can be uncoupled from its function in Pol II pausing. NELFB mutants localized in the cytoplasm and incapacitated in the NELF complex assembly still retain their ability to support cell proliferation and at least part of NELFB-dependent transcriptome. Furthermore, we demonstrate that cytoplasmic NELFB physically and functionally interacts with multiple pro-survival signaling kinases, most notably PI3K/AKT. Enforced activation of PI3K/AKT-related kinases largely rescues deficiency of NELFB-depleted cells in proliferation, but not Pol II pausing. Together, these data revise the current understanding of the growth impact of Pol II pausing and underscore multiplicity of the biological function of individual NELF subunits.

2023-06-30 | GSE205388 | GEO

Essential Signaling Function of Cytoplasmic NELFB Independent of RNA Polymerase II Pausing [ChIP-seq]

2023-06-30 | GSE205504 | GEO

RNA Polymerase II Pausing Factor NELF in CD8+ T Cells Promotes Anti-Tumor Immunity

Project description:The master transcriptional regulator T cell factor 1 (TCF1) is required for the anti-tumor functions of memory and stem-like CD8+ T cells. However, how TCF1 partners with other transcription factors to orchestrate the gene activation program critical for anti-tumor immunity remains poorly understood. Here we show that negative elongation factor B (NELFB), an RNA polymerase II pausing factor, cooperates with TCF1 in T cell responses to cancer. Genetic ablation of mouse Nelfb in mature T lymphocytes severely impaired anti-tumor immunity responding to both primary tumor challenge and tumor antigen-mediated vaccination. NELFB depletion resulted in more exhausted, and reduced memory, T cell populations, whereas its ectopic expression boosted host anti-tumor immunity and efficacy of chimeric antigen receptor (CAR) T-cell immunotherapy. Mechanistically, NELFB is physically associated with TCF1 and recruited preferentially to TCF1-enriched transcriptional enhancers and promoters in CD8+ T cells. Nelfb ablation significantly restricted chromatin accessibility to these TCF1-associated loci. Thus, NELFB is a previously unrecognized functional partner of TCF1 that potentiates the chromatin openness of TCF1-targeting regulatory elements. Our findings also suggest that augmenting NELFB expression in CD8+ T cells may improve therapeutic outcomes of anti-cancer CAR-T immunotherapies.

2022-03-19 | GSE182862 | GEO

Mus musculus

Project description:Wnt & LIF signalling in mESC

| PRJNA106143 | ENA

LIF signaling-dependent gene expression

Project description:Leukemia Inhibitory Factor (LIF) plays an essential role in the maintenance of pluripotency of mouse embryonic stem cells (mESCs). LIF withdrawal induces mESC differentiation. To define noval pluripotent factors downstream of LIF signaling, cDNA microarray was used and seveal well-known pluripotent genes were found to respond to LIF withdrawal, including Klf4, Esrrb, Tbx3, and Prdm14.

2015-06-23 | GSE70104 | GEO

Genome-wide analysis of gene expression in LIF and LIF plus CHIR99021 in C57BL/6 mouse embryonic stem cells(B6 mESCs)

Project description:Analysis of genes induced by CHIR99021 CHIR99021 is a inhibitor of glycogen synthase kinase 3 (GSK3) and can promote B6 mESC sef-renewal when combined with LIF in serum condition. Total RNA obtained from B6 mESCs treated with LIF or LIF/CHIR99021 for 12 hours.

2013-08-29 | E-GEOD-50393 | biostudies-arrayexpress

Genome-wide analysis of the transcriptomes of mouse embryonic stem cells (mESC) maintained in different indicated conditions.

Project description:Analysis of genes involved in the mESC maintainance between different conditions of growth. The hypothesis tested in the present study was that Myc can sustain mESC self renewal and pluripotency. Results provide important information on the mechanism by which Myc supports mESC self renewal, in comparison with the routinely used LIF+serum culture condition, such as a Myc-dependent specific transcriptional program, which involves induction of an alternative Core Regulatory Network, modulation of signallign pathways (Wnt/bcat) and repression of developmental genes. Total RNA obtained from mESC growth 3 days in the indicated condition compared to the routinely used LIF+serum culture condition. Total RNA obtained from EpiSC growth 3 days in standard condition were also used as control for primed stem cell state.

2016-03-31 | E-GEOD-58656 | biostudies-arrayexpress

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