دورية أكاديمية
أعرض في EDS

2-Hydroxyglutarate modulates histone methylation at specific loci and alters gene expression via Rph1 inhibition.

التفاصيل البيبلوغرافية
العنوان: 2-Hydroxyglutarate modulates histone methylation at specific loci and alters gene expression via Rph1 inhibition.
المؤلفون: Gavriil M; https://ror.org/036x5ad56 Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg., Proietto M; https://ror.org/036x5ad56 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg., Paczia N; https://ror.org/036x5ad56 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg., Ginolhac A; https://ror.org/036x5ad56 Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg., Halder R; https://ror.org/036x5ad56 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg., Valceschini E; https://ror.org/036x5ad56 Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg., Sauter T; https://ror.org/036x5ad56 Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg., Linster CL; https://ror.org/036x5ad56 Luxembourg Centre for Systems Biomedicine, University of Luxembourg, Belvaux, Luxembourg carole.linster@uni.lu., Sinkkonen L; https://ror.org/036x5ad56 Department of Life Sciences and Medicine, University of Luxembourg, Belvaux, Luxembourg lasse.sinkkonen@uni.lu.
المصدر: Life science alliance [Life Sci Alliance] 2023 Nov 27; Vol. 7 (2). Date of Electronic Publication: 2023 Nov 27 (Print Publication: 2024).
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Life Science Alliance, LLC Country of Publication: United States NLM ID: 101728869 Publication Model: Electronic-Print Cited Medium: Internet ISSN: 2575-1077 (Electronic) Linking ISSN: 25751077 NLM ISO Abbreviation: Life Sci Alliance Subsets: MEDLINE
أسماء مطبوعة: Original Publication: [Woodbury, NY] : Life Science Alliance, LLC, [2018]-
مواضيع طبية MeSH: Histone Demethylases*/genetics , Histone Demethylases*/metabolism , Saccharomyces cerevisiae*/genetics , Saccharomyces cerevisiae*/metabolism , Saccharomyces cerevisiae Proteins*/genetics , Saccharomyces cerevisiae Proteins*/metabolism, Gene Expression ; Histones/metabolism ; Methylation
مستخلص: 2-Hydroxyglutarate (2-HG) is an oncometabolite that accumulates in certain cancers. Gain-of-function mutations in isocitrate dehydrogenase lead to 2-HG accumulation at the expense of alpha-ketoglutarate. Elevated 2-HG levels inhibit histone and DNA demethylases, causing chromatin structure and gene regulation changes with tumorigenic consequences. We investigated the effects of elevated 2-HG levels in Saccharomyces cerevisiae , a yeast devoid of DNA methylation and heterochromatin-associated histone methylation. Our results demonstrate genetic background-dependent gene expression changes and altered H3K4 and H3K36 methylation at specific loci. Analysis of histone demethylase deletion strains indicated that 2-HG inhibits Rph1 sufficiently to induce extensive gene expression changes. Rph1 is the yeast homolog of human KDM4 demethylases and, among the yeast histone demethylases, was the most sensitive to the inhibitory effect of 2-HG in vitro. Interestingly, Rph1 deficiency favors gene repression and leads to further down-regulation of already silenced genes marked by low H3K4 and H3K36 trimethylation, but abundant in H3K36 dimethylation. Our results provide novel insights into the genome-wide effects of 2-HG and highlight Rph1 as its preferential demethylase target.
(© 2023 Gavriil et al.)
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المشرفين على المادة: 2889-31-8 (alpha-hydroxyglutarate)
EC 1.14.11.- (Histone Demethylases)
0 (Histones)
0 (Saccharomyces cerevisiae Proteins)
0 (RPH1 protein, S cerevisiae)
تواريخ الأحداث: Date Created: 20231127 Date Completed: 20231201 Latest Revision: 20240425
رمز التحديث: 20240425
مُعرف محوري في PubMed: PMC10681907
DOI: 10.26508/lsa.202302333
PMID: 38011998
قاعدة البيانات: MEDLINE
الوصف
تدمد:2575-1077
DOI:10.26508/lsa.202302333