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Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk

BACKGROUND: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding site...

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Autores principales: Ong, Lawrence T. C., Schibeci, Stephen D., Fewings, Nicole L., Booth, David R., Parnell, Grant P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863270/
https://www.ncbi.nlm.nih.gov/pubmed/33541415
http://dx.doi.org/10.1186/s13072-021-00383-x
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author Ong, Lawrence T. C.
Schibeci, Stephen D.
Fewings, Nicole L.
Booth, David R.
Parnell, Grant P.
author_facet Ong, Lawrence T. C.
Schibeci, Stephen D.
Fewings, Nicole L.
Booth, David R.
Parnell, Grant P.
author_sort Ong, Lawrence T. C.
collection PubMed
description BACKGROUND: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol. RESULTS: Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation. CONCLUSION: These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence.
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spelling pubmed-78632702021-02-05 Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk Ong, Lawrence T. C. Schibeci, Stephen D. Fewings, Nicole L. Booth, David R. Parnell, Grant P. Epigenetics Chromatin Research BACKGROUND: The mechanisms linking UV radiation and vitamin D exposure to the risk of acquiring the latitude and critical period-dependent autoimmune disease, multiple sclerosis, is unclear. We examined the effect of vitamin D on DNA methylation and DNA methylation at vitamin D receptor binding sites in adult and paediatric myeloid cells. This was accomplished through differentiating CD34+ haematopoietic progenitors into CD14+ mononuclear phagocytes, in the presence and absence of calcitriol. RESULTS: Few DNA methylation changes occurred in cells treated with calcitriol. However, several VDR-binding sites demonstrated increased DNA methylation in cells of adult origin when compared to cells of paediatric origin. This phenomenon was not observed at other transcription factor binding sites. Genes associated with these sites were enriched for intracellular signalling and cell activation pathways involved in myeloid cell differentiation and adaptive immune system regulation. CONCLUSION: These results suggest vitamin D exposure at critical periods during development may contribute to latitude-related differences in autoimmune disease incidence. BioMed Central 2021-02-04 /pmc/articles/PMC7863270/ /pubmed/33541415 http://dx.doi.org/10.1186/s13072-021-00383-x Text en © The Author(s) 2021 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Ong, Lawrence T. C.
Schibeci, Stephen D.
Fewings, Nicole L.
Booth, David R.
Parnell, Grant P.
Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title_full Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title_fullStr Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title_full_unstemmed Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title_short Age-dependent VDR peak DNA methylation as a mechanism for latitude-dependent multiple sclerosis risk
title_sort age-dependent vdr peak dna methylation as a mechanism for latitude-dependent multiple sclerosis risk
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7863270/
https://www.ncbi.nlm.nih.gov/pubmed/33541415
http://dx.doi.org/10.1186/s13072-021-00383-x
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