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Author Notes:

Corresponding authors: E-mails: soojinyi@gatech.edu; sub@mail.kiz.ac.cn.

Research Funding:

This work was supported by the National Science Foundation (SBE-131719 to SVY), the National Institutes of Health (1R01MH103517-01A1 to SVY, GK and TMP), the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13010000 to BS), the National Natural Science Foundation of China (NSFC 31130051 to BS and NSFC to LS), the Youth Innovation Promotion Association of the Chinese Academy of Sciences (to LS), the Research Personnel Improvement Program by the Department of Education, Language Policy, and Culture by the Basque Government (POS_2013_1_130 to IM); and the Yerkes National Primate Center Base Grant (ORIP/OD P51OD011132).

Keywords:

  • DNA methylation
  • differentially methylated regions
  • epigenomes
  • human brain evolution
  • transcriptional divergence

Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution.

Tools:

Journal Title:

Molecular Biology and Evolution

Volume:

Volume 33, Number 11

Publisher:

, Pages 2947-2959

Type of Work:

Article | Final Publisher PDF

Abstract:

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.

Copyright information:

© The Author 2016.

This is an Open Access work distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/).

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