SIRT6-dependent gene transcriptional profile in human endothelial cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA880643 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR21589900.fastq.gz | Fastqsanger.gz | |||
| SRR21589901.fastq.gz | Fastqsanger.gz | |||
| SRR21589902.fastq.gz | Fastqsanger.gz | |||
| SRR21589903.fastq.gz | Fastqsanger.gz | |||
| SRR21589904.fastq.gz | Fastqsanger.gz |
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Project description:Sirtuin 6 (SIRT6), a well-recognized longevity gene, regulates genome stabilization, DNA repair, inflammation, and metabolic homeostasis. SIRT6 expression is decreased in atherosclerotic lesions from apolipoprotein E deficient mice and human patients. SIRT6 expression is also decreased in endothelial cells (ECs) under chronic stimulation with lipopolysaccharide, hydrogen peroxide and high glucose, three of which are risk factors associated with endothelial dysfunction and atherogenesis. To gain mechanistic insights into the effects of SIRT6 on endothelial gene transcriptome, we performed RNA-sequencing (RNA-seq) analysis of control adenovirus and SIRT6 adenovirus infected human umbilical vein endothelial cells (HUVECs). Gene ontology (GO), pathway enrichment and functional annotation clustering analysis were performed to classify differentially expressed genes and to identify the most significantly enriched GO terms/pathways/gene clusters.
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Project description:We compared the transcriptional profile of mammary tumors spontaneously developed in PyMT transgenic mice either bearing or not additional copies of the endogeneous SIRT6 gene.
2017-01-20 | GSE93837 | GEO
Project description:Obesity is a major health burden. Adipogenesis, the proliferation and differentiation of pree-adipocytes in mature adipocytes, could be a potential therapeutic approach for obesity. Deficiency of SIRT6, a member of the sirtuin family of nicotinamide adenine dinucleotide (NAD)+-dependent protein deacetylases, blocks adipogenesis. New allelic variants of SIRT6 (N308K/A313S) were recently associated with the longevity in Ashkenazi Jews. In this study, we aimed to clarify how these new centenarian-associated SIRT6 genetic variants affect adipogenesis at the transcriptional and epigenetic level. Overexpression of centenarian-associated SIRT6 mutant increased adipogenic differentiation to a similar extent compared to the WT form. However, it triggered distinct histone PTM profiles in mature adipocytes, with significantly higher acetylation levels, and activated divergent transcriptional programs, including those dependent on signaling related to the sympathetic innervation and to PI3K pathway. 3T3-L1 mature adipocytes overexpressing SIRT6 N308K/A313S displayed increased insulin sensitivity in a neuropeptide Y (NPY)-dependent manner.
2024-08-10 | PXD051761 | Pride
Project description:Age-Dependent Transcriptional Alterations in Cardiac Endothelial Cells
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Project description:Atherosclerosis is a focal disease that preferentially develop in the regions of atheroprone disturbed flow, but less in regions of atheroprotective laminar flow. The mechanisms by which atheroprotective laminar flow prevents atherosclerosis at the epigenetic level remain largely unknown. In this study, we observed that laminar flow decreased histone methyltransferase EZH2, which imposes a repressive epigenetic mark of histone 3 lysine 27 trimethylation (H3K27me3) onto target gene promoters, leading to transcriptional silencing. To evaluate the effect of atheroprotective flow on EZH2 and H3K27me3 dependent genome-wide transcriptional profile, we performed RNA-sequencing study on laminar flow and EZH2 siRNA treated human endothelial cells. Venn diagram was used to compare the common regulated genes by both laminar flow and EZH2 depletion. We found atheroprotective flow and EZH2 depletion altere endothelial gene landscape, which include upregulating atheroprotective genes while downregulating pro-atherosclerotic genes.
2017-09-30 | GSE87534 | GEO
Project description:Whole body SIRT6 overexpression (SIRT6-tg) extends lifespan. Here we examine the effect of SIRT6 overexpression on liver mRNA profile
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Project description:Purpose: The complete understanding of how genetic and epigenetic components control beta cell differentiation and function is key to the discovery of novel therapeutic approaches to prevent beta cell dysfunction and failure in the progression of type 2 diabetes. Our goal was to elucidate the role of histone deacetylase SIRT6 in beta-cell development and homeostasis. Methods: The Sirt6 endocrine progenitor cell conditional knockout (EKO) and beta-cell-specific knockout (BKO) mice were generated using the Cre-loxP system. Mice were assayed for islet morphology, glucose tolerance, glucose-stimulated insulin secretion, and susceptibility to streptozotocin. Transcriptional regulatory functions of SIRT6 in primary islets were evaluated by RNA-seq analysis. RT-qPCR and immunoblot were used to verify and investigate the gene expression changes. Chromatin occupancies of SIRT6, H3K9Ac, H3K56Ac, and active RNA Polymerase II were evaluated by chromatin immunoprecipitation. Results: Deletion of Sirt6 in pancreatic endocrine progenitor cells did not affect endocrine morphology, beta cell mass, or insulin production, but did result in glucose intolerance and defective glucose-stimulated insulin secretion in mice. Conditional deletion of Sirt6 in adult beta cells reproduced the insulin secretion defect. Loss of Sirt6 resulted in aberrant upregulation of TXNIP. SIRT6 deficiency led to increased accumulations of H3K9Ac, H3K56Ac, and active RNA polymerase II at the promoter region of Txnip. SIRT6-deficient beta cells exhibited a time-dependent increase of H3K9Ac, H3K56Ac, and TXNIP levels. Furthermore, beta-cell-specific SIRT6 deficient mice showed increased sensitivity to streptozotocin. Conclusions: Our results reveal that SIRT6 suppresses Txnip expression in beta-cells via deacetylation of histone H3 and plays a critical role in maintaining beta-cell function and viability. Agents that preserve SIRT6 activity may be beneficial for preventing the progression of type 2 diabetes.
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2010-06-24 | E-GEOD-13272 | biostudies-arrayexpress
Project description:Sirtuins (Sirt) are a family of enzymes that modify chromatin and other proteins to affect gene activity. Loss of Sirt6 leads to a progeria-like phenotype in mice, but the target of SIRT6 action has been elusive. Here we show that Sirt6 binds to thousands of gene promoters in a stress-inducible fashion, guided by the stress-responsive transcription factor NF-κB. Chromatin profiling by ChIP-chip analysis of Sirt6 and NF-KB component RelA combined with expression array data of wildtype, Sirt6 knockout and Sirt6 RelA double knockout cells demonstrates that RelA recruits Sirt6 to NF-KB targets in response to TNF-a induction and that many of these targets are important for senescence and aging. comparison of wild type, Sirt6-/- and Sirt6-/- RelA-/- MEF cells
2011-05-11 | E-GEOD-28585 | biostudies-arrayexpress
Project description:Chromatin remodeling proteins are frequently dysregulated in human cancer, yet little is known about how they control tumorigenesis. Here, we uncover an epigenetic program mediated by the NAD+-dependent histone deacetylase Sirtuin 6 (SIRT6) that is critical for suppression of pancreatic ductal adenocarcinoma (PDAC), one of the most lethal malignancies. SIRT6 inactivation accelerates PDAC progression and metastasis via upregulation of Lin28b, a negative regulator of the let-7 microRNA. SIRT6 loss results in histone hyperacetylation at the Lin28b promoter, Myc recruitment, and pronounced induction of Lin28b and downstream let-7 target genes, HMGA2, IGF2BP1 and IGF2BP3. This epigenetic program defines a distinct subset representing 30-40% of human PDAC, characterized by poor prognosis and an exquisite dependence on Lin28b for tumor growth. Thus, we identify SIRT6 as an important PDAC tumor suppressor, and uncover the Lin28b pathway as a potential therapeutic target in a molecularlydefined PDAC subset. ChIP-Seq experiments to examine H3K56ac histone modifications in murine PDAC cells that are Sirt6 wild type (WT), Sirt6 knock-out (KO), and Sirt6 KO cells engineered to express Sirt6 WT (Sirt6 KO + Sirt6 WT Restored).
2016-04-01 | E-GEOD-79503 | biostudies-arrayexpress