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The interplay between DNA methylation and sequence divergence in recent human evolution

AutorHernando-Herraez, Irene ; Heyn, Holger; Fernández-Callejo, Marcos; Vidal, Enrique; Fernández-Bellón, Hugo; Prado-Martinez, Javier ; Sharp, Andrew J.; Esteller, Manel; Marqués-Bonet, Tomàs
Palabras claveBinding sites
DNA
DNA methylation
Genome
Histones
Methylation
Nucleotides
Primates
Transcription initiation site
Genetics
Transcription factor
Epigenetics
Hypermethylation
Sorting
Fecha de publicación13-jul-2015
EditorOxford University Press
CitaciónNucleic Acids Research 43(17): 8204-8214 (2015)
ResumenDespite the increasing knowledge about DNA methylation, the understanding of human epigenome evolution is in its infancy. Using whole genome bisulfite sequencing we identified hundreds of differentially methylated regions (DMRs) in humans compared to non-human primates and estimated that ∼25% of these regions were detectable throughout several human tissues. Human DMRs were enriched for specific histone modifications and the majority were located distal to transcription start sites, highlighting the importance of regions outside the direct regulatory context. We also found a significant excess of endogenous retrovirus elements in human-specific hypomethylated. We reported for the first time a close interplay between inter-species genetic and epigenetic variation in regions of incomplete lineage sorting, transcription factor binding sites and human differentially hypermethylated regions. Specifically, we observed an excess of human-specific substitutions in transcription factor binding sites located within human DMRs, suggesting that alteration of regulatory motifs underlies some human-specific methylation patterns. We also found that the acquisition of DNA hypermethylation in the human lineage is frequently coupled with a rapid evolution at nucleotide level in the neighborhood of these CpG sites. Taken together, our results reveal new insights into the mechanistic basis of human-specific DNA methylation patterns and the interpretation of inter-species non-coding variation.
Versión del editorhttps://doi.org/10.1093/nar/gkv693
URIhttp://hdl.handle.net/10261/153234
DOI10.1093/nar/gkv693
ISSN0305-1048
E-ISSN1362-4962
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