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Nestor, C.E.* ; Lentini, A.* ; Hägg Nilsson, C.* ; Gawel, D.R.* ; Gustafsson, M.* ; Mattson, L.* ; Wang, H.* ; Rundquist, O.* ; Meehan, R.R.* ; Klocke, B.* ; Seifert, M.* ; Hauck, S.M. ; Laumen, H. ; Zhang, H.* ; Benson, M.*

5-hydroxymethylcytosine remodeling precedes lineage specification during differentiation of human CD4+ T cells.

Cell Rep. 16, 559-570 (2016)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
Schlagwörter Hematopoietic Stem-cells; Dna Methylation; Autoimmune-disease; Enhancer Activity; Wide Association; Gene-expression; Risk Loci; Tet2; State; 5-methylcytosine
ISSN (print) / ISBN 2211-1247
e-ISSN 2211-1247
Zeitschrift Cell Reports
Quellenangaben Band: 16, Heft: 2, Seiten: 559-570 Artikelnummer: , Supplement: ,
Verlag Cell Press
Verlagsort Cambridge
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) CF Metabolomics & Proteomics (CF-MPC)
CCG Nutrigenomics and Type 2 Diabetes (KKG-KDN)