title: Characterizing the strand-specific distribution of non-CpG methylation in human pluripotent cells.
abstract: DNA methylation is an important defense and regulatory mechanism. In mammals, most DNA methylation occurs at CpG sites, and asymmetric non-CpG methylation has only been detected at appreciable levels in a few cell types. We are the first to systematically study the strand-specific distribution of non-CpG methylation. With the divide-and-compare strategy, we show that CHG and CHH methylation are not intrinsically different in human embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). We also find that non-CpG methylation is skewed between the two strands in introns, especially at intron boundaries and in highly expressed genes. Controlling for the proximal sequences of non-CpG sites, we show that the skew of non-CpG methylation in introns is mainly guided by sequence skew. By studying subgroups of transposable elements, we also found that non-CpG methylation is distributed in a strand-specific manner in both short interspersed nuclear elements (SINE) and long interspersed nuclear elements (LINE), but not in long terminal repeats (LTR). Finally, we show that on the antisense strand of Alus, a non-CpG site just downstream of the A-box is highly methylated. Together, the divide-and-compare strategy leads us to identify regions with strand-specific distributions of non-CpG methylation in humans.
authors.affiliation: Bioinformatics Division and Center for Synthetic & Systems Biology, TNLIST, Tsinghua University, Beijing 100084, China, Department of Molecular and Cell Biology, Center for Systems Biology, The University of Texas at Dallas, Richardson, TX 75080, USA, LMAM, School of Mathematical Sciences, Peking University, Beijing 100871, China, Center for Theoretical Biology, Peking University, Beijing 100871, China and Department of Molecular, Cell and Developmental Biology, University of California, Los Angeles, CA 90095, USA.
authors.forename: Weilong
authors.initials: W
authors.lastname: Guo
authors.forename: Wen-Yu
authors.initials: WY
authors.lastname: Chung
authors.forename: Minping
authors.initials: M
authors.lastname: Qian
authors.forename: Matteo
authors.initials: M
authors.lastname: Pellegrini
authors.forename: Michael Q
authors.initials: MQ
authors.lastname: Zhang
mesh_terms: D002460:Cell Line; D018899:CpG Islands; D019175:DNA Methylation; D006801:Humans; D007438:Introns; D020084:Long Interspersed Nucleotide Elements; D039904:Pluripotent Stem Cells / Q000378:metabolism*; D017422:Sequence Analysis, DNA; D020086:Short Interspersed Nucleotide Elements; D020079:Terminal Repeat Sequences; D014158:Transcription, Genetic