Projects per year
Abstract / Description of output
5-methylcytosine (5mC) is converted to 5-hydroxymethylcytosine (5hmC) by the TET family of enzymes as part of a recently discovered active DNA de-methylation pathway. 5hmC plays important roles in regulation of gene expression and differentiation and has been implicated in T cell malignancies and autoimmunity. Here, we report early and widespread 5mC/5hmC remodeling during human CD4+ T cell differentiation ex vivo at genes and cell-specific enhancers with known T cell function. We observe similar DNA de-methylation in CD4+ memory T cells in vivo, indicating that early remodeling events persist long term in differentiated cells. Underscoring their important function, 5hmC loci were highly enriched for genetic variants associated with T cell diseases and T-cell-specific chromosomal interactions. Extensive functional validation of 22 risk variants revealed potentially pathogenic mechanisms in diabetes and multiple sclerosis. Our results support 5hmC-mediated DNA de-methylation as a key component of CD4+ T cell biology in humans, with important implications for gene regulation and lineage commitment.
Original language | English |
---|---|
Pages (from-to) | 559-70 |
Number of pages | 12 |
Journal | Cell Reports |
Volume | 16 |
Issue number | 2 |
Early online date | 23 Jun 2016 |
DOIs | |
Publication status | Published - 12 Jul 2016 |
Fingerprint
Dive into the research topics of '5-Hydroxymethylcytosine Remodeling Precedes Lineage Specification during Differentiation of Human CD4+ T Cells'. Together they form a unique fingerprint.Projects
- 1 Finished
-
CROATIA PROGRAMME
Wright, A., Adams, I., Aligianis, I., Baldock, R., Bickmore, W., Caceres, J., Dorin, J., Dunlop, M., FitzPatrick, D., Haley, C., Hastie, N., Hill, B., Jackson, I., Jackson, A., Kudla, G., Meehan, R., O'Connell, M., Overton, I., Patton, E., Taylor, M., Tenesa, A. & Van Heyningen, V.
1/04/12 → 31/07/13
Project: Research
Profiles
-
Richard Meehan
- Deanery of Molecular, Genetic and Population Health Sciences - Programme Leader/ Professorial Fellow
- MRC Human Genetics Unit
Person: Academic: Research Active