Comparative Methylome Analyses Identify Epigenetic Regulatory Loci of Human Brain Evolution
| Autor: | Zhe Zhang, Genevieve Konopka, Isabel Mendizabal, Enzhi Hu, Tzung-Fu Hsieh, Soojin V. Yi, Todd M. Preuss, Lei Shi, Bing Su, Thomas Keller |
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| Rok vydání: | 2016 |
| Předmět: |
Male
0301 basic medicine Pan troglodytes Bisulfite sequencing Genomics Biology Genome Epigenesis Genetic Evolution Molecular 03 medical and health sciences transcriptional divergence Genetics Animals Humans Epigenetics Molecular Biology Discoveries Ecology Evolution Behavior and Systematics Epigenomics human brain evolution DNA methylation Brain Biological Evolution Macaca mulatta Chromatin differentially methylated regions 030104 developmental biology Differentially methylated regions Evolutionary biology epigenomes CpG Islands Female Transcriptome |
| Zdroj: | Molecular Biology and Evolution |
| ISSN: | 1537-1719 0737-4038 |
| DOI: | 10.1093/molbev/msw176 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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