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SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [ChIP-Seq]

ABSTRACT: SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [ChIP-Seq]

PROVIDER: PRJNA752643 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15362568_1.fastq.gz	Fastqsanger.gz
	SRR15362568_2.fastq.gz	Fastqsanger.gz
	SRR15362569_1.fastq.gz	Fastqsanger.gz
	SRR15362569_2.fastq.gz	Fastqsanger.gz
	SRR15362570_1.fastq.gz	Fastqsanger.gz

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SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition

Project description:SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition

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SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [RNA-Seq]

Project description:SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [RNA-Seq]

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SIRT6 haploinsufficiency induces BRAFV600E melanoma cell resistance to MAPK inhibitors via IGF signaling

Project description:Through integrated transcriptomic, epigenomic and proteomic analyses, we identified IGFBP2, an insulin growth factor (IGF) binding protein, as a direct SIRT6 target gene. We further show that SIRT6 haploinsufficiency, but not complete knock out of SIRT6 promotes IGFBP2 expression via increased H3K56 acetylation at the IGFBP2 locus allowing melanoma cell survival in the presence of MAPK signaling inhibitors (MAPKi).

2018-08-18 | GSE102813 | GEO

SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition

Project description:This SuperSeries is composed of the SubSeries listed below.

2023-03-15 | GSE181606 | GEO

SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [ChIP-Seq]

Project description:We report a detailed analysis of enhancers marked with H3K27Ac in both basal and classical PDA

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SIRT6 is required for the integrated stress response and resistance to transcriptional inhibition [RNA-Seq]

Project description:We report a detailed analysis of the transcriptomes of both basal and classical PDA treated with THZ1

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SIRT6 phosphorylation - MDM2-mediated degradation of SIRT6 phosphorylated by AKT1 promotes tumorigenesis and trastuzumab resistance in breast cancer

Project description:Sirtuin 6 (SIRT6) is associated with longevity and was recently established as a tumor suppressor. Hence, identifying the molecular regulators of SIRT6 might enable its activation therapeutically in cancer patients. We found that SIRT6 was phosphorylated by the kinase AKT1 at Ser338, which induces its interaction with and ubiquitination by MDM2, priming it for protease-dependent degradation. The survival of patients with breast cancers positively correlated with the abundance of SIRT6 and inversely correlated with the phosphorylation of SIRT6 at Ser338. In a large panel of breast tumor biopsies, SIRT6 abundance inversely correlated with the abundance of phosphorylated AKT. Inhibiting AKT or preventing SIRT6 phosphorylation by mutating Ser338 prevented the degradation of SIRT6 mediated by MDM2, suppressed the proliferation of breast cancer cells in culture, and inhibited the growth of breast tumor xenografts in mice. Overexpressing MDM2 decreased the abundance of SIRT6 in cells, whereas overexpressing an E3 ligase-deficient MDM2 or knocking down endogenous MDM2 increased SIRT6 abundance. Knocking down SIRT6 decreased the sensitivity of a breast cancer cell line to trastuzumab, whereas overexpression of a non-phosphorylatable SIRT6 mutant increased trastuzumab sensitivity in a resistant subculture. Thus, stabilizing SIRT6 may be a clinical strategy for overcoming trastuzumab resistance in breast cancer patients.

2016-07-06 | PXD001154 | Pride

Dynamic Chromatin Localization of Sirt6 Shapes Stress- and Aging- Related Transcriptional Networks (Illumina)

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

SIRT6 maintains redox homeostasis to promote porcine oocyte maturation

Project description:SIRT6, the sixth member of sirtuin family proteins, has been identified as a crucial regulator in multiple molecular pathways related to aging, including genome stability, DNA damage repair, telomere maintenance and inflammation. However, the exact roles of SIRT6 during mammalian oocyte meiosis have not yet fully clarified. Here, we investigated the critical events during porcine oocyte meiotic maturation with the treatment of SIRT6 specific inhibitor SIRT6-IN-1. We found that SIRT6 inhibition resulted in oocyte meiotic failure by displaying the poor expansion of cumulus cells and reduced rate of polar body extrusion. Meanwhile, the compromised spindle assembly, chromosome alignment and actin dynamics were also observed in SIRT6-inhibited oocytes. Moreover, inhibition of SIRT6 led to the defective cytoplasmic maturation by showing the abnormal distribution of cortical granules and their component ovastacin. Notably, we identified that expression of genes related to oocyte meiosis, oxidative phosphorylation and cellular senescence was remarkably altered in SIRT6-inhibited oocytes by transcriptome analysis, and validated that the meiotic defects caused by SIRT6 inhibition resulted from the excessive ROS-induced early apoptosis in oocytes. Taken together, our findings demonstrate that SIRT6 promotes the porcine oocyte meiotic maturation via maintaining the organelle dynamics.

2021-03-16 | GSE161068 | GEO

Sirt6 study

Project description:This SuperSeries is composed of the following subset Series: GSE13206: Human shSIRT6 TNF-alpha timecourse GSE13207: Mouse Sirt6-/- TNF-alpha timecourse GSE13208: Mouse Sirt6-/- tissues GSE13209: Mouse Sirt6-/- RelA+/- tissues Refer to individual Series

2010-06-24 | E-GEOD-13272 | biostudies-arrayexpress

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