Methylation status of nc886 epiallele reflects periconceptional conditions and is associated with glucose metabolism through nc886 RNAs.


Journal

Clinical epigenetics
ISSN: 1868-7083
Titre abrégé: Clin Epigenetics
Pays: Germany
ID NLM: 101516977

Informations de publication

Date de publication:
22 07 2021
Historique:
received: 07 04 2021
accepted: 13 07 2021
entrez: 23 7 2021
pubmed: 24 7 2021
medline: 1 2 2022
Statut: epublish

Résumé

Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines. We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual's methylation status is associated with the mother's age and socioeconomic status, but not with the individual's own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood. These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.

Sections du résumé

BACKGROUND
Non-coding RNA 886 (nc886) is coded from a maternally inherited metastable epiallele. We set out to investigate the determinants and dynamics of the methylation pattern at the nc886 epiallele and how this methylation status associates with nc886 RNA expression. Furthermore, we investigated the associations between the nc886 methylation status or the levels of nc886 RNAs and metabolic traits in the YFS and KORA cohorts. The association between nc886 epiallele methylation and RNA expression was also validated in induced pluripotent stem cell (iPSC) lines.
RESULTS
We confirm that the methylation status of the nc886 epiallele is mostly binomial, with individuals displaying either a non- or hemi-methylated status, but we also describe intermediately and close to fully methylated individuals. We show that an individual's methylation status is associated with the mother's age and socioeconomic status, but not with the individual's own genetics. Once established, the methylation status of the nc886 epiallele remains stable for at least 25 years. This methylation status is strongly associated with the levels of nc886 non-coding RNAs in serum, blood, and iPSC lines. In addition, nc886 methylation status associates with glucose and insulin levels during adolescence but not with the indicators of glucose metabolism or the incidence of type 2 diabetes in adulthood. However, the nc886-3p RNA levels also associate with glucose metabolism in adulthood.
CONCLUSIONS
These results indicate that nc886 metastable epiallele methylation is tuned by the periconceptional conditions and it associates with glucose metabolism through the expression of the ncRNAs coded in the epiallele region.

Identifiants

pubmed: 34294131
doi: 10.1186/s13148-021-01132-3
pii: 10.1186/s13148-021-01132-3
pmc: PMC8296652
doi:

Substances chimiques

RNA, Untranslated 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

143

Subventions

Organisme : Horizon 2020 (Taxinomisis)
ID : 755320
Organisme : German Research Foundation
ID : WA 4081/1-1
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/S020845/1
Pays : United Kingdom
Organisme : Academy of Finland
ID : 134309, 126925, 121584, 124282, 129378, 117787, 41071
Organisme : Academy of Finland
ID : 286284 and 322098
Organisme : Joint Programming Initiative A healthy diet for a healthy life (DIMENSION)
ID : 01EA1902A
Organisme : Horizon 2020 (To_Aition)
ID : 848146
Organisme : Tampere University Hospital Medical Funds
ID : 9X047, 9S054, and 9AB059
Organisme : European Research Council (MULTIEPIGEN)
ID : 742927
Organisme : academy of finland
ID : 285902, 330809 and 338395
Organisme : Tampere University Hospital Medical Funds
ID : X51001

Informations de copyright

© 2021. The Author(s).

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Auteurs

Saara Marttila (S)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland. Saara.Marttila@tuni.fi.
Gerontology Research Center, Tampere University, Tampere, Finland. Saara.Marttila@tuni.fi.

Leena E Viiri (LE)

Heart Group, Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.

Pashupati P Mishra (PP)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Brigitte Kühnel (B)

Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.

Pamela R Matias-Garcia (PR)

Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.

Leo-Pekka Lyytikäinen (LP)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Tiina Ceder (T)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Nina Mononen (N)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Wolfgang Rathmann (W)

German Center for Diabetes Research (DZD), Munich, Neuherberg, Germany.
Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research At Heinrich Heine University, Düsseldorf, Germany.
Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.

Juliane Winkelmann (J)

Institute of Neurogenomics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
Department of Neurogenetics and Institute of Human Genetics, Technical University of Munich, Munich, Germany.

Annette Peters (A)

Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.

Mika Kähönen (M)

Department of Clinical Physiology, Faculty of Medicine and Health Technology, Tampere University and Tampere University Hospital, Tampere, Finland.

Nina Hutri-Kähönen (N)

Tampere Centre for Skills Training and Simulation, Tampere University, Tampere, Finland.

Markus Juonala (M)

Division of Medicine, Department of Medicine, Turku University Hospital, University of Turku, Turku, Finland.

Katriina Aalto-Setälä (K)

Heart Group, Finnish Cardiovascular Research Center, Tampere, Faculty of Medicine and Health Technology, Tampere University, Tampere, Finland.
Heart Hospital, Tampere University Hospital, Tampere University, Tampere, Finland.

Olli Raitakari (O)

Centre for Population Health Research, University of Turku, Turku University Hospital, Turku, Finland.
Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland.
Department of Clinical Physiology and Nuclear Medicine, University of Turku, Turku University Hospital, Turku, Finland.

Terho Lehtimäki (T)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland.

Melanie Waldenberger (M)

Research Unit Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764, Neuherberg, Bavaria, Germany.
Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Bavaria, Germany.
German Centre for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, Munich, Germany.

Emma Raitoharju (E)

Department of Clinical Chemistry, Finnish Cardiovascular Research Center Tampere, Faculty of Medicine and Health Technology, Tampere University, Pirkanmaa Hospital District and Fimlab Laboratories, Tampere, Finland. Emma.Raitoharju@tuni.fi.
Centre for Population Health Research, University of Turku, Turku University Hospital, Turku, Finland. Emma.Raitoharju@tuni.fi.

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