Sökning: onr:"swepub:oai:gup.ub.gu.se/335451" > Altered H3K4me3 pro...
Fältnamn | Indikatorer | Metadata |
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000 | 04021naa a2200493 4500 | |
001 | oai:gup.ub.gu.se/335451 | |
003 | SwePub | |
008 | 240910s2023 | |||||||||||000 ||eng| | |
024 | 7 | a https://gup.ub.gu.se/publication/3354512 URI |
024 | 7 | a https://doi.org/10.1186/s13148-023-01556-z2 DOI |
040 | a (SwePub)gu | |
041 | a eng | |
042 | 9 SwePub | |
072 | 7 | a ref2 swepub-contenttype |
072 | 7 | a art2 swepub-publicationtype |
100 | 1 | a Longo, Michele4 aut |
245 | 1 0 | a Altered H3K4me3 profile at the TFAM promoter causes mitochondrial alterations in preadipocytes from first-degree relatives of type 2 diabetics |
264 | 1 | c 2023 |
520 | a Background First-degree relatives of type 2 diabetics (FDR) exhibit a high risk of developing type 2 diabetes (T2D) and feature subcutaneous adipocyte hypertrophy, independent of obesity. In FDR, adipose cell abnormalities contribute to early insulin-resistance and are determined by adipocyte precursor cells (APCs) early senescence and impaired recruitment into the adipogenic pathway. Epigenetic mechanisms signal adipocyte differentiation, leading us to hypothesize that abnormal epigenetic modifications cause adipocyte dysfunction and enhance T2D risk. To test this hypothesis, we examined the genome-wide histone profile in APCs from the subcutaneous adipose tissue of healthy FDR.Results Sequencing-data analysis revealed 2644 regions differentially enriched in lysine 4 tri-methylated H3-histone (H3K4me3) in FDR compared to controls (CTRL) with significant enrichment in mitochondrial-related genes. These included TFAM, which regulates mitochondrial DNA (mtDNA) content and stability. In FDR APCs, a significant reduction in H3K4me3 abundance at the TFAM promoter was accompanied by a reduction in TFAM mRNA and protein levels. FDR APCs also exhibited reduced mtDNA content and mitochondrial-genome transcription. In parallel, FDR APCs exhibited impaired differentiation and TFAM induction during adipogenesis. In CTRL APCs, TFAM-siRNA reduced mtDNA content, mitochondrial transcription and adipocyte differentiation in parallel with upregulation of the CDKN1A and ZMAT3 senescence genes. Furthermore, TFAM-siRNA significantly expanded hydrogen peroxide (H2O2)-induced senescence, while H2O2 did not affect TFAM expression.Conclusions Histone modifications regulate APCs ability to differentiate in mature cells, at least in part by modulating TFAM expression and affecting mitochondrial function. Reduced H3K4me3 enrichment at the TFAM promoter renders human APCs senescent and dysfunctional, increasing T2D risk. | |
650 | 7 | a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi0 (SwePub)302032 hsv//swe |
650 | 7 | a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology0 (SwePub)302032 hsv//eng |
653 | a Type 2 diabetes | |
653 | a Adipose tissue dysfunction | |
653 | a Epigenetic mechanisms | |
653 | a Mitochondrial alterations | |
653 | a Adipogenesis | |
653 | a Premature senescence | |
700 | 1 | a Zatterale, Federica4 aut |
700 | 1 | a Spinelli, Rosa4 aut |
700 | 1 | a Naderi, Jamal4 aut |
700 | 1 | a Parrillo, Luca4 aut |
700 | 1 | a Florese, Pasqualina4 aut |
700 | 1 | a Nigro, Cecilia4 aut |
700 | 1 | a Leone, Alessia4 aut |
700 | 1 | a Moccia, Augusta4 aut |
700 | 1 | a Desiderio, Antonella4 aut |
700 | 1 | a Raciti, Gregory A.4 aut |
700 | 1 | a Miele, Claudia4 aut |
700 | 1 | a Smith, Ulf,d 1943u Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine4 aut0 (Swepub:gu)xsmiul |
700 | 1 | a Beguinot, Francesco4 aut |
710 | 2 | a Göteborgs universitetb Institutionen för medicin, avdelningen för molekylär och klinisk medicin4 org |
773 | 0 | t CLINICAL EPIGENETICSg 15:1q 15:1x 1868-7075x 1868-7083 |
856 | 4 8 | u https://gup.ub.gu.se/publication/335451 |
856 | 4 8 | u https://doi.org/10.1186/s13148-023-01556-z |
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