Existence and possible roles of independent non-CpG methylation in the mammalian brain |
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| Authors: | Jong-Hun Lee Yutaka Saito Sung-Joon Park Kenta Nakai |
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| Affiliation: | Human Genome Center, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan;Artificial Intelligence Research Center, National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan;AIST-Waseda University Computational Bio Big-Data Open Innovation Laboratory (CBBD-OIL), Tokyo, Japan;Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan |
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| Abstract: | Methylated non-CpGs (mCpHs) in mammalian cells yield weak enrichment signals and colocalize with methylated CpGs (mCpGs), thus have been considered byproducts of hyperactive methyltransferases. However, mCpHs are cell type-specific and associated with epigenetic regulation, although their dependency on mCpGs remains to be elucidated. In this study, we demonstrated that mCpHs colocalize with mCpGs in pluripotent stem cells, but not in brain cells. In addition, profiling genome-wide methylation patterns using a hidden Markov model revealed abundant genomic regions in which CpGs and CpHs are differentially methylated in brain. These regions were frequently located in putative enhancers, and mCpHs within the enhancers increased in correlation with brain age. The enhancers with hypermethylated CpHs were associated with genes functionally enriched in immune responses, and some of the genes were related to neuroinflammation and degeneration. This study provides insight into the roles of non-CpG methylation as an epigenetic code in the mammalian brain genome. |
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| Keywords: | Non-CpG methylation hidden Markov model neuro-epigenetics |
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