DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome
Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies...
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Frontiers Media S.A.
2022-04-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2022.792165/full |
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| author | Francesco Ravaioli Michele Zampieri Luca Morandi Luca Morandi Chiara Pirazzini Camilla Pellegrini Sara De Fanti Sara De Fanti Noémie Gensous Noémie Gensous Gian Luca Pirazzoli Luisa Sambati Alessandro Ghezzo Fabio Ciccarone Anna Reale Daniela Monti Stefano Salvioli Paola Caiafa Miriam Capri Alexander Bürkle Maria Moreno-Villanueva Paolo Garagnani Paolo Garagnani Paolo Garagnani Paolo Garagnani Claudio Franceschi Maria Giulia Bacalini |
| author_facet | Francesco Ravaioli Michele Zampieri Luca Morandi Luca Morandi Chiara Pirazzini Camilla Pellegrini Sara De Fanti Sara De Fanti Noémie Gensous Noémie Gensous Gian Luca Pirazzoli Luisa Sambati Alessandro Ghezzo Fabio Ciccarone Anna Reale Daniela Monti Stefano Salvioli Paola Caiafa Miriam Capri Alexander Bürkle Maria Moreno-Villanueva Paolo Garagnani Paolo Garagnani Paolo Garagnani Paolo Garagnani Claudio Franceschi Maria Giulia Bacalini |
| author_sort | Francesco Ravaioli |
| collection | DOAJ |
| description | Control of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome. |
| first_indexed | 2024-04-14T01:30:22Z |
| format | Article |
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| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-14T01:30:22Z |
| publishDate | 2022-04-01 |
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| series | Frontiers in Genetics |
| spelling | doaj.art-c2b89720e67247efbd271f664858ee072022-12-22T02:20:12ZengFrontiers Media S.A.Frontiers in Genetics1664-80212022-04-011310.3389/fgene.2022.792165792165DNA Methylation Analysis of Ribosomal DNA in Adults With Down SyndromeFrancesco Ravaioli0Michele Zampieri1Luca Morandi2Luca Morandi3Chiara Pirazzini4Camilla Pellegrini5Sara De Fanti6Sara De Fanti7Noémie Gensous8Noémie Gensous9Gian Luca Pirazzoli10Luisa Sambati11Alessandro Ghezzo12Fabio Ciccarone13Anna Reale14Daniela Monti15Stefano Salvioli16Paola Caiafa17Miriam Capri18Alexander Bürkle19Maria Moreno-Villanueva20Paolo Garagnani21Paolo Garagnani22Paolo Garagnani23Paolo Garagnani24Claudio Franceschi25Maria Giulia Bacalini26Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, ItalyFunctional and Molecular Neuroimaging Unit, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, ItalyIRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyIRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyDepartment of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, ItalyInterdepartmental Centre Alma Mater Research Institute on Global Challenges and Climate Change, University of Bologna, Bologna, ItalyDepartment of Internal Medicine and Clinical Immunology, CHU Bordeaux (Groupe Hospitalier Saint-André), Bordeaux, FranceUMR/CNRS 5164, ImmunoConcEpT, CNRS, University of Bordeaux, Bordeaux, France0Medical Department, Maggiore Hospital, Bologna, Italy1IRCCS Istituto Delle Scienze Neurologiche di Bologna, U.O.C. Clinica Neurologica Rete Neurologica Metropolitana (NEUROMET), Bologna, Italy2DIMES, School of Medicine, University of Bologna, Bologna, Italy3IRCCS San Raffaele Roma, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, Rome, Italy4Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy5Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, ItalyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy6Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany6Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, GermanyDepartment of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy7Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy8CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”—Unit of Bologna, Bologna, Italy9Department of Laboratory Medicine, Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden0Laboratory of Systems Medicine of Healthy Aging, Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, RussiaIRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, ItalyControl of ribosome biogenesis is a critical aspect of the regulation of cell metabolism. As ribosomal genes (rDNA) are organized in repeated clusters on chromosomes 13, 14, 15, 21, and 22, trisomy of chromosome 21 confers an excess of rDNA copies to persons with Down syndrome (DS). Previous studies showed an alteration of ribosome biogenesis in children with DS, but the epigenetic regulation of rDNA genes has not been investigated in adults with DS so far. In this study, we used a targeted deep-sequencing approach to measure DNA methylation (DNAm) of rDNA units in whole blood from 69 adults with DS and 95 euploid controls. We further evaluated the expression of the precursor of ribosomal RNAs (RNA45S) in peripheral blood mononuclear cells (PBMCs) from the same subjects. We found that the rDNA promoter tends to be hypermethylated in DS concerning the control group. The analysis of epihaplotypes (the combination of methylated and unmethylated CpG sites along the same DNA molecule) showed a significantly lower intra-individual diversity in the DS group, which at the same time was characterized by a higher interindividual variability. Finally, we showed that RNA45S expression is lower in adults with DS. Collectively, our results suggest a rearrangement of the epigenetic profile of rDNA in DS, possibly to compensate for the extranumerary rDNA copies. Future studies should assess whether the regulation of ribosome biogenesis can contribute to the pathogenesis of DS and explain the clinical heterogeneity characteristic of the syndrome.https://www.frontiersin.org/articles/10.3389/fgene.2022.792165/fullDown syndromeribosomal genesrDNAagingDNA methylation |
| spellingShingle | Francesco Ravaioli Michele Zampieri Luca Morandi Luca Morandi Chiara Pirazzini Camilla Pellegrini Sara De Fanti Sara De Fanti Noémie Gensous Noémie Gensous Gian Luca Pirazzoli Luisa Sambati Alessandro Ghezzo Fabio Ciccarone Anna Reale Daniela Monti Stefano Salvioli Paola Caiafa Miriam Capri Alexander Bürkle Maria Moreno-Villanueva Paolo Garagnani Paolo Garagnani Paolo Garagnani Paolo Garagnani Claudio Franceschi Maria Giulia Bacalini DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome Frontiers in Genetics Down syndrome ribosomal genes rDNA aging DNA methylation |
| title | DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome |
| title_full | DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome |
| title_fullStr | DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome |
| title_full_unstemmed | DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome |
| title_short | DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome |
| title_sort | dna methylation analysis of ribosomal dna in adults with down syndrome |
| topic | Down syndrome ribosomal genes rDNA aging DNA methylation |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2022.792165/full |
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