%0 Journal Article
%T Resources for methylome analysis suitable for gene knockout studies of potential epigenome modifiers
%A Gareth A Wilson
%A Pawandeep Dhami
%A Andrew Feber
%A Daniel Cortš¢zar
%A Yuka Suzuki
%A Reiner Schulz
%A Primo Sch£¿r
%A Stephan Beck
%J GigaScience
%D 2012
%I BioMed Central
%R 10.1186/2047-217x-1-3
%X We report genome-wide DNA methylation profiles of wild type (wt) and mutant mouse cells, comprising 3 biological replicates of Thymine DNA glycosylase (Tdg) knockout (KO) embryonic stem cells (ESCs), in vitro differentiated neural precursor cells (NPCs) and embryonic fibroblasts (MEFs). The resulting 18 methylomes were analysed with MeDUSA (Methylated DNA Utility for Sequence Analysis), a novel MeDIP-seq computational analysis pipeline for the identification of differentially methylated regions (DMRs). The observed increase of hypermethylation in MEF promoter-associated CpG islands supports a previously proposed role for Tdg in the protection of regulatory regions from epigenetic silencing. Further analysis of genes and regions associated with the DMRs by gene ontology, pathway, and ChIP analyses revealed further insights into Tdg function, including an association of TDG with low-methylated distal regulatory regions.We demonstrate that MeDUSA is able to detect both large-scale changes between cells from different stages of differentiation and also small but significant changes between the methylomes of cells that only differ in the KO of a single gene. These changes were validated utilising publicly available datasets and confirm TDG's function in the protection of regulatory regions from epigenetic silencing.DNA methylation is an important epigenetic modification, playing a vital role in genome dynamics. In conjunction with histone modifications, remodeling complexes and non-coding RNAs, it modulates chromatin density and thereby accessibility of the underlying DNA to the transcriptional machinery. As a result, DNA methylation is involved in a diverse range of processes including embryogenesis, genomic imprinting, cellular differentiation, DNA-protein interactions, and gene regulation [1].In mammalian genomes, methylation predominantly occurs symmetrically on both DNA strands at palindromic CpG dinucleotides, but the preference between CpG and non-CpG methylation
%K Methylome
%K MeDIP-seq
%K Epigenetics
%K Epigenomics
%K DNA methylation
%K Computational pipeline
%K MeDUSA
%U http://www.gigasciencejournal.com/content/1/1/3