Abstract：
: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.
journal_name
Cell Repjournal_title
Cell reportsauthors
Nestor CE,Lentini A,Hägg Nilsson C,Gawel DR,Gustafsson M,Mattson L,Wang H,Rundquist O,Meehan RR,Klocke B,Seifert M,Hauck SM,Laumen H,Zhang H,Benson Mdoi
10.1016/j.celrep.2016.05.091subject
Has Abstractpub_date
2016-07-12 00:00:00pages
559-570issue
2issn
2211-1247pii
S2211-1247(16)30704-5journal_volume
16pub_type
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