Regulation of the methylome in differentiation from adult stem cells may underpin vitamin D risk in MS
- Resource Type
- Authors
- Kelly Veale; David R. Booth; Graeme J. Stewart; Christopher Liddle; Grant P Parnell; Lawrence T C Ong
- Source
- Genes and immunity. 21(5)
- Subject
- 0301 basic medicine
Adult
Male
Multiple Sclerosis
Immunology
Biology
Monocytes
03 medical and health sciences
Epigenome
0302 clinical medicine
Genetics
Vitamin D and neurology
Humans
Nuclear Receptor Co-Repressor 2
Progenitor cell
Vitamin D
Genetics (clinical)
Methylation
DNA Methylation
Middle Aged
Hematopoietic Stem Cells
Molecular biology
Hematopoiesis
Killer Cells, Natural
Haematopoiesis
030104 developmental biology
DNA methylation
Receptors, Calcitriol
CpG Islands
Female
Stem cell
Vitamin D receptor binding
030215 immunology
Adult stem cell
HLA-DRB1 Chains
Protein Binding
Transcription Factors
- Language
- ISSN
- 1476-5470
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.