Sparse conserved under-methylated CpGs are associated with high-order chromatin structure

Xueqiu Lin, Jianzhong Su, Kaifu Chen, Benjamin Rodriguez, Wei Li

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Background: Whole-genome bisulfite sequencing (WGBS) is the gold standard for studying landscape DNA methylation. Current computational methods for WGBS are mainly designed for gene regulatory regions with multiple under-methylated CpGs (UMCs), such as promoters and enhancers. Results: To reliably predict the functional importance of single isolated UMCs across the genome, which is usually not achievable using traditional methods, we develop a multi-sample-based method. We identified 9421 sparse conserved under-methylated CpGs (scUMCs) from 31 high-quality methylomes, which are enriched in distal interacting anchor regions co-occupied by multiple chromatin-loop factors and are flanked by highly methylated CpGs. Moreover, cell lineage-specific scUMCs are associated with essential developmental genes, regulators of cell differentiation, and chromatin remodeling enzymes. Dynamic methylation levels of scUMCs correlate with the intensity of chromatin interactions and binding of looping factors as well as patterns of gene expression. Conclusions: We introduce an innovative computational method for the identification of scUMCs, which are novel epigenetic features associated with high-order chromatin structure, opening new directions in the study of the inter-relationships between DNA methylation and chromatin structure.

Original languageEnglish (US)
Article number163
JournalGenome Biology
Issue number1
StatePublished - Aug 31 2017


  • Chromatin structure
  • Chromatin-loop factors
  • DNA methylation
  • Interacting anchor
  • Multi-sample-based method
  • Sparse conserved under-methylated CpG
  • Whole-genome bisulfite sequencing

ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Genetics
  • Cell Biology


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