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Project description:JUNB transcriptional regulation in cell cycle control and tumorigenic cell invasion
| PRJNA802847 | ENA
Project description:BackgroundJUNB transcription factor contributes to the formation of the ubiquitous transcriptional complex AP-1 involved in the control of many physiological and disease-associated functions. The roles of JUNB in the control of cell division and tumorigenic processes are acknowledged but still unclear.ResultsHere, we report the results of combined transcriptomic, genomic, and functional studies showing that JUNB promotes cell cycle progression via induction of cyclin E1 and repression of transforming growth factor (TGF)-β2 genes. We also show that high levels of JUNB switch the response of TGF-β2 stimulation from an antiproliferative to a pro-invasive one, induce endogenous TGF-β2 production by promoting TGF-β2 mRNA translation, and enhance tumor growth and metastasis in mice. Moreover, tumor genomic data indicate that JUNB amplification associates with poor prognosis in breast and ovarian cancer patients.ConclusionsOur results reveal novel functions for JUNB in cell proliferation and tumor aggressiveness through regulation of cyclin E1 and TGF-β2 expression, which might be exploited for cancer prognosis and therapy.
| S-EPMC9733061 | biostudies-literature
Project description:Type 1 diabetes (T1D) is a metabolic disease resulting from progressive autoimmune destruction of insulin-producing pancreatic beta cells. Although the majority of beta cells are lost in T1D, a small subset undergoes senescence, a stress response involving growth arrest, DNA damage response, and activation of a senescence-associated secretory phenotype (SASP). SASP in beta cells of the nonobese diabetic (NOD) mouse model of T1D and primary human islets is regulated at the level of transcription by bromodomain extra-terminal (BET) proteins, but the mechanisms remain unclear. To explore how SASP is transcriptionally regulated in beta cells, we used the NOD beta cell line NIT-1 to model beta cell SASP and identified binding partners of BET protein Brd4 and explored the role of the cyclin-dependent kinase inhibitor p21. Brd4 interacted with a variety of proteins in senescent NIT-1 cells including subunits of the Ino80 chromatin remodeling complex, which was expressed in beta cells during T1D progression in NOD mice and in human beta cells of control, autoantibody-positive, and T1D donors as determined from single-cell RNA-seq data. RNAi knockdown of p21 during senescence in NIT-1 cells did not significantly impact viability or SASP. Taken together, these results suggest that Brd4 interacts with several protein partners during senescence in NIT-1 cells, some of which may play roles in SASP gene activation and that p21 is dispensable for the SASP in this beta cell model.
| S-EPMC10968907 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2012-12-01 | E-GEOD-42402 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-05-04 | E-GEOD-46608 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2020-07-21 | GSE151172 | GEO
Project description:Precise regulation of the cell cycle of embryonic stem cells (ESCs) is critical for their self-maintenance and differentiation. The cell cycle of ESCs differs from that of somatic cells and is different depending on the cell culture conditions. However, the cell cycle regulation in ESCs via epigenetic mechanisms remains unclear. Here, we showed that the ATP-dependent chromatin remodeler Ino80 regulates the cell cycle genes in ESCs under primed conditions. Ino80 loss led to a significantly extended length of the G1-phase in ESCs grown under primed culture conditions. Ino80 directly bound to the transcription start site and regulated the expression of cell cycle-related genes. Furthermore, Ino80 loss induced cell apoptosis. However, the regulatory mechanism of Ino80 in differentiating ESC cycle slightly differed; an extended S-phase was detected in differentiating inducible Ino80 knockout ESCs. RNA-seq analysis of differentiating ESCs revealed that the expression of genes associated with organ development cell cycle is persistently altered in Ino80 knockout cells, suggesting that cell cycle regulation by Ino80 is not limited to undifferentiated ESCs. Therefore, our study establishes the function of Ino80 in ESC cycle via transcriptional regulation, at least partly. Moreover, this Ino80 function may be universal to other cell types.
| S-EPMC9740483 | biostudies-literature
Project description:Progression of the Caulobacter cell cycle requires temporal and spatial control of gene expression, culminating in an asymmetric cell division yielding distinct daughter cells. To explore the contribution of translational control, RNA-seq and ribosome profiling were used to assay global transcription and translation levels of individual genes at six times over the cell cycle. Translational efficiency (TE) was used as a metric for the relative rate of protein production from each mRNA. TE profiles with similar cell cycle patterns were found across multiple clusters of genes, including those in operons or in subsets of operons. Collections of genes associated with central cell cycle functional modules (e.g., biosynthesis of stalk, flagellum, or chemotaxis machinery) have consistent but different TE temporal patterns, independent of their operon organization. Differential translation of operon-encoded genes facilitates precise cell cycle-timing for the dynamic assembly of multiprotein complexes, such as the flagellum and the stalk and the correct positioning of regulatory proteins to specific cell poles. The cell cycle-regulatory pathways that produce specific temporal TE patterns are separate from-but highly coordinated with-the transcriptional cell cycle circuitry, suggesting that the scheduling of translational regulation is organized by the same cyclical regulatory circuit that directs the transcriptional control of the Caulobacter cell cycle.
| S-EPMC5098616 | biostudies-literature
Project description:Many questions remain about the interplay between adaptive and neutral processes leading to genome expansion and the evolution of cellular complexity. Genome size appears to be tightly linked to the size of the regulatory repertoire of cells (van Nimwegen E. 2003. Scaling laws in the functional content of genomes. Trends Gen. 19(9):479-484). In the context of gene regulation, we here study the interplay between adaptive and nonadaptive forces on genome and regulatory network in a computational model of cell-cycle adaptation to different environments. Starting from the well-known Caulobacter crescentus network, we report on ten replicate in silico evolution experiments where cells evolve cell-cycle control by adapting to increasingly harsh spatial habitats. We find adaptive expansion of the regulatory repertoire of cells. Having a large genome is inherently costly, but also allows for improved cell-cycle behavior. Replicates traverse different evolutionary trajectories leading to distinct eco-evolutionary strategies. In four replicates, cells evolve a generalist strategy to cope with a variety of nutrient levels; in two replicates, different specialist cells evolve for specific nutrient levels; in the remaining four replicates, an intermediate strategy evolves. These diverse evolutionary outcomes reveal the role of contingency in a system under strong selective forces. This study shows that functionality of cells depends on the combination of regulatory network topology and genome organization. For example, the positions of dosage-sensitive genes are exploited to signal to the regulatory network when replication is completed, forming a de novo evolved cell cycle checkpoint. Our results underline the importance of the integration of multiple organizational levels to understand complex gene regulation and the evolution thereof.
| S-EPMC9086953 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-10-01 | E-GEOD-51279 | biostudies-arrayexpress