The Sequence Preference in DNA Methylation Level and Its Structural Basis in Mammalian

【作者】 高毅勤； 张玲； 古婵；

【机构】 北京大学；

【摘要】 Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The methylation level distribution is bimodal. Here, we develop an algorithm to quantify the bimodal methylation level distribution and find that in the tetranucleotides 5’-NCGB-3’(N=A, C, G or T and B=A, C, G or T), GCGB and CCGB show more apparent bimodalities than ACGB and TCGB. Such a finding indicates that GCGB and CCGB are less variant in the level of methylation. The degrees of bimodalities of NCGB are conserved among different cells, tissues and species, indicating common features in the mechanisms of methylation and demethylation, presumably mediated by DNMTs and TETs in mammalians, respectively. Using MD simulations, we find that the DNA intrinsic structure properties of CpG/5 mC p G sites are indeed significantly affected by the flanking sequences N and B, in NXGB(X=C or 5 mC). In accordance with the sequencing data analysis, compared with GXGB and CXGB, AXGB and TXGB adopt conformations biased toward base flipping, thus are proposed to be more active for methylation and demethylation.更多还原

【Abstract】 Methylation of cytosine at the 5 position of the pyrimidine ring is the most prevalent and significant epigenetic modifications in mammalian DNA. The methylation level distribution is bimodal. Here, we develop an algorithm to quantify the bimodal methylation level distribution and find that in the tetranucleotides 5’-NCGB-3’(N=A, C, G or T and B=A, C, G or T), GCGB and CCGB show more apparent bimodalities than ACGB and TCGB. Such a finding indicates that GCGB and CCGB are less variant in the level of methylation. The degrees of bimodalities of NCGB are conserved among different cells, tissues and species, indicating common features in the mechanisms of methylation and demethylation, presumably mediated by DNMTs and TETs in mammalians, respectively. Using MD simulations, we find that the DNA intrinsic structure properties of CpG/5 mC p G sites are indeed significantly affected by the flanking sequences N and B, in NXGB(X=C or 5 mC). In accordance with the sequencing data analysis, compared with GXGB and CXGB, AXGB and TXGB adopt conformations biased toward base flipping, thus are proposed to be more active for methylation and demethylation.更多还原