Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites.
Chenhuan XuVictor G CorcesPublished in: Science (New York, N.Y.) (2018)
The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation. Finally, we show the inheritance of hemiCpGs at short regions flanking CCCTC-binding factor (CTCF)/cohesin binding sites in pluripotent cells. Elimination of hemimethylation causes reduced frequency of chromatin interactions emanating from these sites, suggesting a role for hemimethylation as a stable epigenetic mark regulating CTCF-mediated chromatin interactions.
Keyphrases
- dna methylation
- gene expression
- genome wide
- circulating tumor
- cell free
- mitochondrial dna
- induced apoptosis
- single molecule
- copy number
- high resolution
- dna damage
- transcription factor
- nucleic acid
- signaling pathway
- endoplasmic reticulum stress
- public health
- single cell
- circulating tumor cells
- dna binding
- binding protein
- cell proliferation
- cancer therapy
- pi k akt