title: Age-Dependent Decrease of DNA Hydroxymethylation in Human T Cells.
abstract: Hydroxymethylcytosine (hmC) is a natural nucleobase, which is converted from methylcytosine (mC) by tet methylcytosine dioxygenase (TET) family (TET1-3) enzymes. Decrease of genomic hmC is postulated to confer a risk for myeloid-lineage as well as T-cell neoplasms, based on the fact that loss-of-function mutations in the TET2 gene were frequently identified in these diseases. The relationship between hmC and aging remains to be elucidated. Here, we demonstrated that hmC content decreased with age in the peripheral blood T cells of 53 human volunteers. We further identified that the mRNA expression levels of TET1 and TET3 decreased with age, while those of TET2 were not influenced by age. The genomic hmC content was correlated with the mRNA expression level of TET3, but not those of TET1 and TET2. Our study suggests the presence of new epigenetic regulatory mechanisms in aging T cells.
authors.affiliation: Department of Hematology, Graduate School of Comprehensive Human Science, University of Tsukuba.
authors.forename: Thien Phu
authors.initials: TP
authors.lastname: Truong
authors.forename: Mamiko
authors.initials: M
authors.lastname: Sakata-Yanagimoto
authors.forename: Momoko
authors.initials: M
authors.lastname: Yamada
authors.forename: Genta
authors.initials: G
authors.lastname: Nagae
authors.forename: Terukazu
authors.initials: T
authors.lastname: Enami
authors.forename: Rie
authors.initials: R
authors.lastname: Nakamoto-Matsubara
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics; D049308:Dioxygenases / Q000235:genetics; D044127:Epigenesis, Genetic; D015870:Gene Expression; D064368:Healthy Volunteers; D006801:Humans; D008875:Middle Aged; D006899:Mixed Function Oxygenases; D011518:Proto-Oncogene Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013601:T-Lymphocytes / Q000378:metabolism*; D055815:Young Adult
chemical_list: D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D006899:Mixed Function Oxygenases; C462539:TET1 protein, human; C578792:TET3 protein, human; D049308:Dioxygenases