RT Journal
A1 Feng, Yan
A1 Zhang, Zhiqiang
A1 Hong, Yuyang
A1 Ding, Yi
A1 Liu, Leiqin
A1 Gao, Siqi
A1 Fang, Hai
A1 Shi, Jiantao
T1 A DNA methylation haplotype block landscape in human tissues and preimplantation embryos reveals regulatory elements defined by comethylation patterns
JF Genome Research 
JO Genome Research 
YR 2023 
FD December 01 
VO 33 
IS 12 
SP 2041 
OP 2052 
DO 10.1101/gr.278146.123 
UL http://genome.cshlp.org/content/33/12/2041.abstract 
AB DNA methylation and associated regulatory elements play a crucial role in gene expression regulation. Previous studies have focused primarily on the distribution of mean methylation levels. Advances in whole-genome bisulfite sequencing (WGBS) have enabled the characterization of DNA methylation haplotypes (MHAPs), representing CpG sites from the same read fragment on a single chromosome, and the subsequent identification of methylation haplotype blocks (MHBs), in which adjacent CpGs on the same fragment are comethylated. Using our expert-curated WGBS data sets, we report comprehensive landscapes of MHBs in 17 representative normal somatic human tissues and during early human embryonic development. Integrative analysis reveals MHBs as a distinctive type of regulatory element characterized by comethylation patterns rather than mean methylation levels. We show the enrichment of MHBs in open chromatin regions, tissue-specific histone marks, and enhancers, including super-enhancers. Moreover, we find that MHBs tend to localize near tissue-specific genes and show an association with differential gene expression that is independent of mean methylation. Similar findings are observed in the context of human embryonic development, highlighting the dynamic nature of MHBs during early development. Collectively, our comprehensive MHB landscapes provide valuable insights into the tissue specificity and developmental dynamics of DNA methylation.