TAILIEUCHUNG - Báo cáo y học: "A comparative analysis of DNA methylation across human embryonic stem cell lines"

Tuyển tập các báo cáo nghiên cứu về y học được đăng trên tạp chí y học Wertheim cung cấp cho các bạn kiến thức về ngành y đề tài: A comparative analysis of DNA methylation across human embryonic stem cell lines. | Chen et al. Genome Biology 2011 12 R62 http 2011 12 7 R62 Genome Biology RESEARCH Open Access A comparative analysis of DNA methylation across human embryonic stem cell lines Pao-Yang Chen1 2 Suhua Feng1 Jong Wha Joanne Joo3 Steve E Jacobsen1 4 5 and Matteo Pellegrini1 5 6 Abstract Background We performed a comparative analysis of the genome-wide DNA methylation profiles from three human embryonic stem cell HESC lines. It had previously been shown that HESC lines had significantly higher non-CG methylation than differentiated cells and we therefore asked whether these sites were conserved across cell lines. Results We find that heavily methylated non-CG sites are strongly conserved especially when found within the motif TACAG. They are enriched in splice sites and are more methylated than other non-CG sites in genes. We next studied the relationship between allele-specific expression and allele-specific methylation. By combining bisulfite sequencing and whole transcriptome shotgun sequencing RNA-seq data we identified 1 020 genes that show allele-specific expression and 14 of CG sites genome-wide have allele-specific methylation. Finally we asked whether the methylation state of transcription factor binding sites affects the binding of transcription factors. We identified variations in methylation levels at binding sites and found that for several transcription factors the correlation between the methylation at binding sites and gene expression is generally stronger than in the neighboring sequences. Conclusions These results suggest a possible but as yet unknown functional role for the highly methylated conserved non-CG sites in the regulation of HESCs. We also identified a novel set of genes that are likely transcriptionally regulated by methylation in an allele-specific manner. The analysis of transcription factor binding sites suggests that the methylation state of cis-regulatory elements impacts the ability of factors to bind and regulate .

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