Regulation of the methylome in differentiation from adult stem cells may underpin vitamin D risk in MS.
Adult
CpG Islands
DNA Methylation
Epigenome
Female
HLA-DRB1 Chains
/ genetics
Hematopoiesis
Hematopoietic Stem Cells
/ cytology
Humans
Killer Cells, Natural
/ cytology
Male
Middle Aged
Monocytes
/ cytology
Multiple Sclerosis
/ genetics
Nuclear Receptor Co-Repressor 2
/ genetics
Protein Binding
Receptors, Calcitriol
/ metabolism
Transcription Factors
/ genetics
Vitamin D
/ metabolism
Journal
Genes and immunity
ISSN: 1476-5470
Titre abrégé: Genes Immun
Pays: England
ID NLM: 100953417
Informations de publication
Date de publication:
11 2020
11 2020
Historique:
received:
04
02
2020
accepted:
28
09
2020
revised:
31
08
2020
pubmed:
11
10
2020
medline:
13
8
2021
entrez:
10
10
2020
Statut:
ppublish
Résumé
Multiple lines of evidence indicate Multiple Sclerosis (MS) is affected by vitamin D. This effect may be mediated by methylation in immune cell progenitors. We aimed to determine (1) if haematopoietic stem cell methylation constrains methylation in daughter cells and is variable between individuals, and (2) the interaction of methylation with the vitamin D receptor binding sites. We interrogated genomic methylation levels from matching purified CD34+ haematopoietic stem cells and progeny CD14+ monocytes and CD56+ NK cells from 11 individuals using modified reduced representation bisulfite sequencing. Differential methylation of Vitamin D Receptor binding sites and MS risk genes was assessed from this and using pyrosequencing for the vitamin D regulated MS risk gene ZMIZ1. Although DNA methylation states at CpG islands and other sites are almost entirely recapitulated between progenitor and progeny immune cells, significant variation was detected at some regions between cell subsets and individuals; including around the MS risk genes HLA DRB1 and the vitamin D repressor NCOR2. Methylation of the vitamin D responsive MS risk gene ZMIZ1 was associated with risk SNP and disease. We conclude that DNA methylation settings in adult haematopoietic stem cells may contribute to individual variation in vitamin D responses in immune cells.
Identifiants
pubmed: 33037402
doi: 10.1038/s41435-020-00114-4
pii: 10.1038/s41435-020-00114-4
doi:
Substances chimiques
HLA-DRB1 Chains
0
NCOR2 protein, human
0
Nuclear Receptor Co-Repressor 2
0
Receptors, Calcitriol
0
Transcription Factors
0
ZMIZ1 protein, human
0
Vitamin D
1406-16-2
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
335-347Références
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