Measuring CpG Methylation by SMRT Sequencing

Y. Suzuki1, J. Korlach2, S. Morishita1

1The University of Tokyo, Tokyo, japan; 2Pacific Biosciences, Menlo Park, CA, United States


There has been a great deal of interest in identification of genome-wide epigenetic DNA modifications in recent years, because DNA modifications play an essential role in cellular and developmental processes (Anway, Cupp, Uzumcu, & Skinner, 2005; jirtle & Skinner, 2007; Miller, 2010; Molaro et al., 2011; Qu et al., 2012; Schmitz et al., 2011; Smith et al., 2012; Weaver et al., 2004; Zemach, McDaniel, Silva, & Zilberman, 2010). Some human transposable elements (TEs), such as long interspersed nuclear elements (LINEs), are reported to transpose actively within somatic cells along differentiation of neural tissues, and to be partly regulated by DNA methylation (Muotri et al., 2005, 2010). One study showed that each family of human TEs is in a variety of methylation statuses according to tissue type by looking at the mixture of methylation information on the consensus sequence of TEs in the same family (Xie et al., 2013). Many human diseases are associated with the disruption of DNA modifications. In particular, hypo- methylation of repetitive elements, such as LINE-1 elements, has been also related to some cancers (Ross, Rand, & Molloy, 2010; Wilson, Power, & Molloy, 2007). Although only a few LINE-1 elements exhibit activity in the human genome (Beck et al., 2010), transpositions of these elements have been reported in various cancer genomes (Goodier, 2014; Lee et al., 2012), and importantly, it has been reported that transpositions are correlated with hypomethylation of the promoter region of LINE-1 elements (Tubio et al., 2014). Therefore, it is essential to develop an experimental framework that can characterize the methylation state of repetitive elements in a genome-wide manner.

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