Characterization of MyDNMT1 and Changes of Global DNA Methylation during the Embryonic Development in Mizuhopecten yessoensis

DNA methylation is a critical epigenetic mechanism that influences gene transcription, genomic stability, X-chromosome inactivation and other factors, and appropriate DNA methylation is crucial in development. DNA methyltransferase 1 （DNMT1） plays an important role in maintaining the established methylation pattern during DNA replication. Although the effect of DNA methylation on embryonic development has been well known in vertebrates, little research has been carried out in invertebrates, especially in marine bivalves. In this study, the DNMT1 gene （MyDNMT1） was firstly identified from Mizuhopecten yessoensis. The full-length cDNA of MyDNMT1 was 5 039 bp, consisted of a 5＇ untranslated region （5＇-UTR） of 79 bp, a 3＇ untranslated region （3＇-UTR） of 199 bp, and a 4 761 bp open reading frame （ORF） encoding a peptide of 1 586 amino acids without a putative signal peptide. The relative mRNA expression level of MyDNMT1 was measured during the embryonic development of M. ydssoensis using real-time PCR, which revealed that the level at stage zygote and trochophore were significantly higher than that at other stages. We further examined the global DNA methylation during development by colorimetric method. The results showed that the methylation level was increased and reached the peak at blastula stage, then dramatically decreased, and fluctuated at early D-shaped larva stage. This study provided greater insight into the DNA methylation of embryonic development, which obtained a better understanding of the relationship between the DNA methylation and the embryonic development in bivalve mollusks.

DNA methylation in the genesis,progress and prognosis of head and neck cancer

Epigenetic alteration studies in cancer research have been progressing rapidly in recent years.DNA methylation,including DNA hypermethylation and DNA hypomethylation,is one of the main epigenetic alterations in head and neck cancer development.Here,we review recent advances in DNA methylation and factors affecting DNA methylation,including DNA methylation enzymes,HPV status and smoking and drinking habits,in the field of head and neck cancer occurrence,progression,metastasis,and prognosis,hoping to shed light on how DNA methylation interacts with head and neck cancer and lay a foundation for future prognosis prediction and therapy.

DNMT3A/3B overexpression might be correlated with poor patient survival, hypermethylation and low expression of ESR1/PGR in endometrioid carcinoma: an analysis of The Cancer Genome Atlas

Background:DNA methylation is involved in numerous biologic events and associates with transcriptional gene silencing, playing an important role in the pathogenesis of endometrial cancer.ESR1/PGR frequently undergoes de novo methylation and loss expression in a wide variety of tumors, including breast, colon, lung, and brain tumors.However, the mechanisms underlying estrogen and progesterone receptors (ER/PR) loss in endometrial cancer have not been studied extensively.The aims of this study were to determine the expression of DNA (cytosine-5)-methyltransferase 3A/3B (DNMT3A/3B) in endometrial cancer to investigate whether the methylation catalyzed by DNMT3A/3B contributes to low ER/PR expression.Methods:The clinicopathologic information and RNA-Seq expression data of DNMT3A/3B of 544 endometrial cancers were derived from The Cancer Genome Atlas (TCGA) uterine cancer cohort in May 2018.RNA-Seq level of DNMT3A/3B was compared between these clinicopathologic factors with t-test or one-way analysis of variance.Results:DNMT3A/3B was overexpressed in endometrioid carcinoma (EEC) and was even higher in non-endometrioid carcinoma (NEEC) (DNMT3A, EEC vs.NEEC:37.6% vs.69.9%, t=-7.440, P<0.001;DNMT3B, EEC vs.NEEC:42.4% vs.72.8 %, t=-6.897, P<0.001).In EEC, DNMT3A overexpression was significantly correlated with the hypermethylation and low expression of the ESR1 and PGR (P<0.05).The same trend was observed in the DNMT3B overexpression subgroup.In the ESR1/PGR low-expression subgroups, as much as 83.1% of ESR1 and 59.5% of PGR were hypermethylated, which was significantly greater than the ESR1/PGR high-expression subgroups (31.3% and 11.9%, respectively).However, the above phenomena were absent in NEEC, while DNMT3A/3B overexpression, ESR1/PGR hypermethylation, and low ER/PR expression occurred much more often.In univariate analysis, DNMT3A/3B overexpressions were significantly correlated with worse prognosis.In multivariate analysis, only DNMT3A was an independent predictor of disease-free survival (P<0.05).Conclusions:DNMT3A/3B expression increases progressively from EEC to NEEC and is correlated with poor survival.The mechanisms underlying low ER/PR expression might be distinct in EEC vs.NEEC.In EEC, methylation related to DNMT3A/3B overexpression might play a major role in ER/PR downregulation.