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Induced pluripotent stem cells (iPSCs) show variable methylation patterns between lines, some of which reflect aberrant differences relative to embryonic stem cells (ESCs). To examine whether this aberrant methylation results from genetic variation or non-genetic mechanisms, we generated human iPSCs from monozygotic twins to investigate how genetic background, clone, and passage number contribute. We found that aberrantly methylated CpGs are enriched in regulatory regions associated with MYC protein motifs and affect gene expression. We classified differentially methylated CpGs as being associated with genetic and/or non-genetic factors (clone and passage), and we found that aberrant methylation preferentially occurs at CpGs associated with clone-specific effects. We further found that clone-specific effects play a strong role in recurrent aberrant methylation at specific CpG sites across different studies. Our results argue that a non-genetic biological mechanism underlies aberrant methylation in iPSCs and that it is likely based on a probabilistic process involving MYC that takes place during or shortly after reprogramming.

Background: Fibrillin-1 (FBN1) methylation risk from control to colorectal cancer (CRC), the variation regularities of FBN1 methylation, and DNA methyltransferase (DNMT) catalyzed with FBN1 methylation had not been reported yet; these were all studied in this paper. Methods: FBN1 methylation roles were investigated with big data and meta-analysis. Results: The 6 independent studies were searched including 702 tissue and 448 feces. FBN1 methylation frequencies of CRC, adenoma or polyp, and control in tissue were 79.1%, 69.4%, and 2.7%, respectively; those in feces were 74.6%, 50.7%, and 10.8%, respectively. FBN1 methylation of control samples was used as a standard reference; this study showed that ORs (95% CI) of FBN1 methylation in CRC and control tissues were 124.79 (62.86–248.35); those in feces were detected to be 30.87 (16.48–57.85). FBN1 methylation risk in tissue was higher than that in feces; there was a quadratic equation between the methylation rate of tissue and that of feces. There was another quadratic curve in the variation process of FBN1 methylation; this curve reflected the overall metabolism regularity of DNMT. Conclusions: The transcriptional inactivation of FBN1 gene might start from normal colonic epithelium; the quadratic curve of FBN1 methylation catalyzed by DNMT can gradually produce powerful strength, accelerate expansion, and eventually lead to CRC. The overall metabolism regularity of DNMT maintains the changing process of FBN1 methylation; it has the changing feature of the same quadratic curve. FBN1 methylation is a promising biomarker. FBN1 methylation risk size in feces reflects that in tissue in non-invasive detection. [ABSTRACT FROM AUTHOR]

BackgroundFibrillin-1 (FBN1) methylation risk from control to colorectal cancer (CRC), the variation regularities of FBN1 methylation, and DNA methyltransferase (DNMT) catalyzed with FBN1 methylation had not been reported yet; these were all studied in this paper.MethodsFBN1 methylation roles were investigated with big data and meta-analysis.ResultsThe 6 independent studies were searched including 702 tissue and 448 feces. FBN1 methylation frequencies of CRC, adenoma or polyp, and control in tissue were 79.1%, 69.4%, and 2.7%, respectively; those in feces were 74.6%, 50.7%, and 10.8%, respectively. FBN1 methylation of control samples was used as a standard reference; this study showed that ORs (95% CI) of FBN1 methylation in CRC and control tissues were 124.79 (62.86–248.35); those in feces were detected to be 30.87 (16.48–57.85). FBN1 methylation risk in tissue was higher than that in feces; there was a quadratic equation between the methylation rate of tissue and that of feces. There was another quadratic curve in the variation process of FBN1 methylation; this curve reflected the overall metabolism regularity of DNMT.ConclusionsThe transcriptional inactivation of FBN1 gene might start from normal colonic epithelium; the quadratic curve of FBN1 methylation catalyzed by DNMT can gradually produce powerful strength, accelerate expansion, and eventually lead to CRC. The overall metabolism regularity of DNMT maintains the changing process of FBN1 methylation; it has the changing feature of the same quadratic curve. FBN1 methylation is a promising biomarker. FBN1 methylation risk size in feces reflects that in tissue in non-invasive detection.

Sweet orange is an important group of citrus cultivars, which includes a number of bud sport cultivars. Little is known about the CpG methylation status of the CCGG sequences in the orange genome. In this study, methylation-sensitive amplification polymorphism (MSAP), based on the application of isoschizomers ( Hpa II and Msp I), was first used to analyze cytosine methylation patterns in 57 orange cultivars that were not fully differentiated by regular DNA molecular markers. Three types of bands were generated from ten primer pairs. Type I bands were present following restriction with Eco RI + Hpa II and Eco RI + Msp I; type II or type III were present only following restriction with either Eco RI + Hpa II or with Eco RI + Msp I. The total number of these three types of bands was 802, 72, and 157, respectively. Among these, the number of polymorphic bands were 244 (30.2%), 23 (31.9%), and 32 (20.4%), in type I, II and III, respectively. The methylation patterns of these 57 cultivars are discussed and assessed by dendrograms derived from the analysis of polymorphic MSAP bands. The distribution of polymorphic bands of the above three types demonstrate the methylation patterns and frequency at the cytosine loci. We suggest that methylation events could be more frequent than demethylation events, and that the methylation patterns maybe associated with phenotypic traits. [ABSTRACT FROM AUTHOR]