DNA Methylation Analysis of Ribosomal DNA in Adults With Down Syndrome

Frontiers in Genetics

Claudio Franceschi¹  Gian Luca Pirazzoli²  Luisa Sambati³  Alessandro Ghezzo⁴  Fabio Ciccarone⁵  Daniela Monti⁶  Paola Caiafa⁷  Alexander Bürkle⁸  Maria Moreno-Villanueva⁸  Paolo Garagnani^1,11  Luca Morandi^1,13  Michele Zampieri^1,14  Anna Reale^1,14  Francesco Ravaioli^1,15  Miriam Capri^1,15  Stefano Salvioli^1,15  Maria Giulia Bacalini^1,18  Camilla Pellegrini^1,18  Chiara Pirazzini^1,18  Sara De Fanti^1,19  Noémie Gensous^2,20 

[1] 0Laboratory of Systems Medicine of Healthy Aging, Department of Applied Mathematics, Lobachevsky University, Nizhny Novgorod, Russia;0Medical Department, Maggiore Hospital, Bologna, Italy;1IRCCS Istituto Delle Scienze Neurologiche di Bologna, U.O.C. Clinica Neurologica Rete Neurologica Metropolitana (NEUROMET), Bologna, Italy;2DIMES, School of Medicine, University of Bologna, Bologna, Italy;3IRCCS San Raffaele Roma, Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, Rome, Italy;4Department of Experimental and Clinical Biomedical Sciences “Mario Serio”, University of Florence, Florence, Italy;5Department of Cellular Biotechnologies and Haematology, Sapienza University of Rome, Rome, Italy;6Molecular Toxicology Group, Department of Biology, University of Konstanz, Konstanz, Germany;7Applied Biomedical Research Center (CRBA), S. Orsola-Malpighi Polyclinic, Bologna, Italy;8CNR Institute of Molecular Genetics “Luigi Luca Cavalli-Sforza”—Unit of Bologna, Bologna, Italy;9Department of Laboratory Medicine, Clinical Chemistry, Karolinska Institutet, Karolinska University Hospital, Huddinge, Sweden;Department of Biological, Geological and Environmental Sciences, University of Bologna, Bologna, Italy;Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy;Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy;Department of Experimental, Diagnostic and Specialty Medicine (DIMES), University of Bologna, Bologna, Italy;Department of Internal Medicine and Clinical Immunology, CHU Bordeaux (Groupe Hospitalier Saint-André), Bordeaux, France;Functional and Molecular Neuroimaging Unit, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy;IRCCS Istituto Delle Scienze Neurologiche di Bologna, Bologna, Italy;Interdepartmental Centre Alma Mater Research Institute on Global Challenges and Climate Change, University of Bologna, Bologna, Italy;UMR/CNRS 5164, ImmunoConcEpT, CNRS, University of Bordeaux, Bordeaux, France;

关键词: Down syndrome;    ribosomal genes;    rDNA;    aging;    DNA methylation;   

DOI  :  10.3389/fgene.2022.792165

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown