Nelfb promotes dWAT formation through RNA Polymerase II-mediated adipogenic gene regulation
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE291112 | GEO | 2025/03/07
REPOSITORIES: GEO
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Project description:Nelfb promotes dWAT formation through RNA Polymerase II-mediated adipogenic gene regulation
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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
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.
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Project description:The transcriptional mechanisms by which temporary exposure to developmental signals instigates adipocyte differentiation are unknown. During early adipogenesis, we find transient enrichment of the glucocorticoid receptor (GR), CCAAT/enhancer binding protein b (CEBPb), p300, mediator subunit 1, and histone H3 acetylation near genes involved in cell proliferation, development and differentiation, including the gene encoding the master regulator of adipocyte differentiation, peroxisome proliferator activated receptor g2 (PPARg2). Occupancy and enhancer function are triggered by adipogenic signals, and diminish upon their removal. GR, which is required for adipogenesis but need not be active in the mature adipocyte, transiently functions with other enhancer proteins to propagate a new program of gene expression that includes induction of PPARg2, thereby providing a memory of the earlier adipogenic signal. Thus, the conversion of preadipocyte to adipocytes involves the formation of an epigenomic transition state that is not observed in cells at the beginning or end of the differentiation process. Genomic occupancy profiled by high throughput sequencing (ChIP-seq) from 3T3-L1 cells during differentiation for H3K9Ac, CEBPb and GR.
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2022-06-17 | GSE176020 | GEO
Project description:Inherent depot- and age-dependent preadipocyte characteristics may contribute to age-related fat redistribution. Both aging and depot origin affect preadipocyte replication and adipogenesis. To define responsible mechanisms, we analyzed genome-wide expression profiles in epididymal (E) and perirenal (P) preadipocytes cultured from young (3 month) and old (30m) rats. Differences between depots were distinct from and more dramatic than those that occur with aging. Experiment Overall Design: Preadipocytes were isolated from perirenal and epididymal fat depots of 3 young (3 month) and 3 old (30 month) Brown Norway rats for a total of 12 samples from 6 different animals.
2008-06-15 | E-GEOD-6699 | biostudies-arrayexpress
Project description:The transcriptional mechanisms by which temporary exposure to developmental signals instigates adipocyte differentiation are unknown. During early adipogenesis, we find transient enrichment of the glucocorticoid receptor (GR), CCAAT/enhancer binding protein b (CEBPb), p300, mediator subunit 1, and histone H3 acetylation near genes involved in cell proliferation, development and differentiation, including the gene encoding the master regulator of adipocyte differentiation, peroxisome proliferator activated receptor g2 (PPARg2). Occupancy and enhancer function are triggered by adipogenic signals, and diminish upon their removal. GR, which is required for adipogenesis but need not be active in the mature adipocyte, transiently functions with other enhancer proteins to propagate a new program of gene expression that includes induction of PPARg2, thereby providing a memory of the earlier adipogenic signal. Thus, the conversion of preadipocyte to adipocytes involves the formation of an epigenomic transition state that is not observed in cells at the beginning or end of the differentiation process.
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