Abstract

Defects in epigenetic mechanisms are well-recognized in multiple neurodevelopmental disorders including Schizophrenia (SZ). In addition to aberrant epigenetic marks, dysregulated epigenetic machinery was also identified among the contributory factors in SZ patients. Among these, overexpression of DNA methyltransferase 1 (DNMT1) was the first to be identified. In this context, Dnmt1tet/tet (Tet/Tet), a mouse embryonic stem cell (ESC) line that overexpresses DNMT1 in ESCs and neurons, was developed to study abnormal neurogenesis. In an attempt to understand whether DNMT1 overexpression is associated with aberrant DNA methylation, we compared the genome-wide methylation levels of R1 (wild-type) and Tet/Tet ESCs and their neuronal derivatives by RRBS. The RRBS data (GSE152817) showed an average mappability of ∼59% and an average coverage of 40X per locus. The data was processed to determine the methylation percentages of target genes and was visualized using the UCSC genome browser. The observed methylation differences were validated by Combined Bisulfite Restriction Analysis (COBRA). The methylome data described here can be used to study the relationship between DNMT1 overexpression, alterations in methylation levels and dysregulation of SZ-associated genes.

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