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论文题目: Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution
作者: Isabel Mendizabal; Lei Shi; Thomas E. Keller; Genevieve Konopka; Todd M. Preuss; Tzung-Fu Hsieh; Enzhi Hu; Zhe Zhang; Bing Su*; Soojin V. Yi*
联系作者: soojinyi@gatech.edu; sub@mail.kiz.ac.cn
外单位作者单位:
发表年度: 2016
卷: 33
期: 11
页码: 2947-2959
摘要:

How do epigenetic modifications change across species and how do these modifications affect evolution? These are fundamental questions at the forefront of our evolutionary epigenomic understanding. Our previous work investigated human and chimpanzee brain methylomes, but it was limited by the lack of outgroup data which is critical for comparative (epi)genomic studies. Here we compared whole genome DNA methylation maps from brains of humans, chimpanzees and also rhesus macaques (outgroup) to elucidate DNA methylation changes during human brain evolution. Moreover, we validated that our approach is highly robust by further examining 38 human-specific DMRs using targeted deep genomic and bisulfite sequencing in an independent panel of 37 individuals from five primate species. Our unbiased genome-scan identified human brain differentially methylated regions (DMRs), irrespective of their associations with annotated genes. Remarkably, over half of the newly identified DMRs locate in intergenic regions or gene bodies. Nevertheless, their regulatory potential is on par with those of promoter DMRs. An intriguing observation is that DMRs are enriched in active chromatin loops, suggesting human-specific evolutionary remodeling at a higher-order chromatin structure. These findings indicate that there is substantial reprogramming of epigenomic landscapes during human brain evolution involving noncoding regions.

刊物名称: Molecular Biology and Evolution
论文出处: http://mbe.oxfordjournals.org/content/33/11/2947
影响因子: 13.649 (2015)