Human Protein Kinase C Beta I

The DNA methylation age, a good reflection of human aging process, has been used to predict chronological age of adults and newborns. However, the prediction model for children and adolescents was absent. In this study, we aimed to generate a prediction model of chronological age for children and adolescents aged 6-17 years by using age-specific DNA methylation patterns from 180 Chinese twin individuals. We identified 6,350 age-related CpGs from the epigenome-wide association analysis (N=179). 116 known age-related sites in children were confirmed. 83 novel CpGs were selected as predictors from all age-related loci by elastic net regression and they could accurately predict the chronological age of the pediatric population, with a correlation of 0.99 and the error of 0.23 years in the training dataset (N=90). The predictive accuracy in the testing dataset (N=89) was high (correlation=0.93, error=0.62 years). Among the 83 predictors, 49 sites were novel probes not existing on the Illumina 450K BeadChip. The top two predictors of age were on the PRKCB and REG4 genes, which are associated with diabetes and cancer, respectively. Our results suggest that the chronological age can be accurately predicted among children and adolescents aged 6-17 years by 83 newly identified CpG sites.

Adult T-cell leukemia (ATL) is an aggressive T-cell malignancy caused by human T-cell leukemia virus type 1 (HTLV-1) that develops through a multistep carcinogenesis process involving 5 or more genetic events. We provide a comprehensive overview of recently uncovered information on the molecular basis of leukemo-genesis in ATL. Broadly, the landscape of genetic abnormalities in ATL that include alterations highly enriched in genes for T-cell receptor-NF-kappa B signaling such as PLCG1, PRKCB, and CARD11 and gain-of function mutations in CCR4 and CCR7. Conversely, the epigenetic landscape of ATL can be summarized as polycomb repressive complex 2 hyperactivation with genome-wide H3K27 me3 accumulation as the basis of the unique transcriptome of ATL cells. Expression of H3K27 methyltransferase enhancer of zeste 2 was shown to be induced by HTLV-1 Tax and NF-kappa B. Furthermore, provirus integration site analysis with high-throughput sequencing enabled the analysis of clonal composition and cell number of each clone in vivo, whereas multicolor flow cytometric analysis with CD7 and cell adhesion molecule 1 enabled the identification of HTLV-1-infected CD4+ T cells in vivo. Sorted immortalized but untransformed cells displayed epigenetic changes closely overlapping those observed in terminally transformed ATL cells, suggesting that epigenetic abnormalities are likely earlier events in leukemo-genesis. These new findings broaden the scope of conceptualization of the molecular mechanisms of leukemogenesis, dissecting them into immortalization and clonal progression. These recent findings also open a new direction of drug development for ATL prevention and treatment because epigenetic marks can be reprogrammed. Mechanisms underlying initial immortalization and progressive accumulation of these abnormalities remain to be elucidated. (Blood. 2017; 129(9): 1071-1081)