Methylation QTLs Are Associated with Coordinated Changes in Transcription Factor Binding, Histone Modifications, and Gene Expression Levels


DNA methylation is an important epigenetic mark that contributes to many biological processes including the regulation of gene expression. Genetic variation has been associated with quantitative changes in DNA methylation (meQTLs). We identified thousands of meQTLs using an assay that allowed us to measure methylation levels at around 300 thousand cytosines. We found that meQTLs are enriched with loci that is also associated with quantitative changes in gene expression, DNase I hypersensitivity, PolII occupancy, and a number of histone marks. This suggests that many molecular events are likely regulated in concert. Finally, we found that changes in transcription factor binding as well as transcription factor abundance are associated with changes in DNA methylation near transcription factor binding sites. This work contributes to our understanding of the regulation of DNA methylation in the larger context of gene regulatory landscape.


Vyšlo v časopise: Methylation QTLs Are Associated with Coordinated Changes in Transcription Factor Binding, Histone Modifications, and Gene Expression Levels. PLoS Genet 10(9): e32767. doi:10.1371/journal.pgen.1004663
Kategorie: Research Article
prolekare.web.journal.doi_sk: 10.1371/journal.pgen.1004663

Souhrn

DNA methylation is an important epigenetic mark that contributes to many biological processes including the regulation of gene expression. Genetic variation has been associated with quantitative changes in DNA methylation (meQTLs). We identified thousands of meQTLs using an assay that allowed us to measure methylation levels at around 300 thousand cytosines. We found that meQTLs are enriched with loci that is also associated with quantitative changes in gene expression, DNase I hypersensitivity, PolII occupancy, and a number of histone marks. This suggests that many molecular events are likely regulated in concert. Finally, we found that changes in transcription factor binding as well as transcription factor abundance are associated with changes in DNA methylation near transcription factor binding sites. This work contributes to our understanding of the regulation of DNA methylation in the larger context of gene regulatory landscape.


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