Dataset Information

Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity.

ABSTRACT: Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected. The simultaneous deletion of phosphatase and tensin homolog (Pten) elevated the level of phosphorylated AKT and rescued many of the morphological defects and cell death in DNMT1-deficient lenses. With a different Cre driver (MLR10) we demonstrated that a small number of lens epithelial cells escaped Dnmt1-deletion and over-proliferated to compensate for the loss of Dnmt1-deleted cells, suggesting that lens epithelium possess a substantial capacity for self-renewal. Unlike lenses deficient for Dnmt1, inactivation of both Dnmt3a and Dnmt3b by either the Le-Cre or MLR10-Cre transgene did not result in any obvious lens phenotype prior to 10 months of age. Taken together, while lens epithelial cell survival requires DNMT1, morphologically normal lenses develop in the absence of both DNMT3A and DNMT3B.

SUBMITTER: Hoang TV

PROVIDER: S-EPMC5270636 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity.

Hoang Thanh V TV Horowitz Evan R ER Chaffee Blake R BR Qi Peipei P Flake Rachel E RE Bruney Devin G DG Rasor Blake J BJ Rosalez Savana E SE Wagner Brad D BD Robinson Michael L ML

Epigenetics 20161108 1

Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens ...[more]

PMID: 27824296

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Project description:BackgroundIncreasing studies showed that abnormal changes in single nucleotide polymorphisms (SNPs) of DNMTs (DNMT1, DNMT3A and DNMT3B) were associated with occurrence or decrease of various tumors. However, the associations between DNMTs variations and gastric cancer (GC) risk were still conflicting. We aimed to assess the effect of DNMTs polymorphisms on the susceptibility to GC.MethodsFirstly, we did a meta-analysis for 7 SNPs (rs16999593, rs2228611, rs8101866 in DNMT1, rs1550117, rs13420827 in DNMT3A, rs1569686, rs2424913 in DNMT3B). Four genetic models (homozygote, heterozygote, dominant and recessive model) were used. Moreover, a meta-sensitivity and subgroup analysis was performed to clarify heterogeneity source. Lastly, 17 SNPs that couldn't be meta-analyzed were presented in a systematic review.Findings20 studies were included, 13 studies could be meta-analyzed and 7 ones could not. Firstly, a meta-analysis on 13 studies (3959 GC cases and 5992 controls) for 7 SNPs showed that GC risk increased in rs16999593 (heterozygote model: OR 1.36, 95%CI 1.14-1.61; dominant model: OR 1.36, 95%CI 1.15-1.60) and rs1550117 (homozygote model: OR 2.03, 95%CI 1.38-3.00; dominant model: OR 1.20, 95%CI 1.01-1.42; recessive model: OR 1.96, 95%CI 1.33-2.89) but decreased in rs1569686 (dominant model: OR 0.74, 95%CI 0.61-0.90). The remaining SNPs were not found associated with GC risk. Furthermore, the subgroup analysis indicated that for rs1550117 and rs1569686, the significant associations were particularly found in people from Chinese Jiangsu province (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.48, 95%CI 0.36-0.64) and that PCR-RFLP was a sensitive method to discover significant associations (rs1550117, OR 1.77, 95%CI 1.25-2.51; rs1569686, OR 0.49, 95%CI 0.37-0.65). Lastly, a systematic review on 7 studies for 17 SNPs suggested that rs36012910, rs7560488 and rs6087990 might have a potential effect on GC initiation.ConclusionThis meta-analysis demonstrated that rs16999593 and rs1550117 could contribute to GC risk and that rs1569686 might be a protective factor against gastric carcinogenesis. By using these SNPs as biomarkers, it is feasible to estimate the risk of acquiring GC and thus formulate timely preventive strategy.

Dataset Information

Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity.

Publications

Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity.

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