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
Similar Datasets
Project description:Nelfb promotes dWAT formation through RNA Polymerase II-mediated adipogenic gene regulation
| PRJNA1231624 | ENA
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.
2023-06-30 | GSE205504 | GEO
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.
2010-05-20 | E-GEOD-21898 | biostudies-arrayexpress
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. Keywords: cell type and age comparison
2008-01-09 | GSE6699 | GEO
Project description:Obesity and associated metabolic outcomes define the metabolic syndrome. Interestingly, an under-appreciated fact is that body fat distribution, rather than total body fat amount, is a key determinant of metabolic disease. Indeed, in contrast to upper-body obesity, lower-body fat accumulation inversely correlates with metabolic risks. Understanding processes regulating upper- vs. lower-body fat expansion is paramount to predict (and prevent) these risks. We combine functional, proteomics, transcriptomics and epigenomics analyses to identify chromatin-associated mechanisms of adipose depot-specific fat expansion. Here, we analyze by RNA-seq the transcriptome of adipose stem cells (ASCs) from gluteal (lower-body) and abdominal subcutaneous (upper-body) depots induced to differentiate in vitro towards the adipogenic lineage. We aim to identify adipose depot-specific and temporal differences in the up- or down-regulation of gene expression, and a later stage relate these differences to changes in chromatin states.
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.
2010-05-20 | GSE21898 | GEO
Project description:Global gene expression analysis was performed to investigate the changes of the fibroblast phenotype after four-week inductions toward adipocytic, osteoblastic and chondrocytic lineages. Human cells. Differential gene regulation, interpreted through Gene Set Enrichment Analysis, highlight important similarities and differences of induced fibroblasts compared to control cultures of human fibroblasts, adipocytes, osteoblasts and articular chondrocytes. Fibroblast controls were compared to Adipogenic induced fibroblasts and adipocytes. Gene sets were analysed with GSEA (webgestalt). Repeated for each lineage.
2012-03-01 | E-GEOD-35545 | biostudies-arrayexpress
Project description:Surface topography impacts on cell growth and differentiation, but it is not trivial to generate homogeneous surface structures and to define the specific morphological parameters of relevance. In this study, we have compared gene expression profiles of mesenchymal stem cells (MSCs) on nanostructured groove/ridge surfaces. Patterns were generated in polyimide using multi beam laser interference. These structures affected cell size and orientation of human MSCs. Furthermore, the nano-patterns with a periodicity of 650 nm increased differentiation towards osteogenic and adipogenic lineages. However, in absence of differentiation media the surface structures did neither induce differentiation, nor lineage-specific gene expression changes – as assessed by genome wide gene expression profiles with Affymetrix microarray technology. Our results demonstrate that grooves and ridges at a periodicity of 650 nm enhance the propensity of MSCs to differentiate towards adipogenic and/or osteogenic lineages – but they do not directly govern lineage-specific gene expression changes. 9 samples were hybridized to the GeneChip Human Gene 2.0 ST Array (Affymetrix). In comparison to the manuscript the donor IDs refer as follows: donor 1 = AT57; donor 2 = AT58; donor 3 = AT61.
2015-08-25 | E-GEOD-61113 | biostudies-arrayexpress