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Intervals of unmethylated DNA spatially co-segregate in cis and in trans [WGBS]

ABSTRACT: High order chromatin structure and DNA methylation are implicated in multiple development processes and diseases. Despite the recent developments of methods studying high order chromatin interactions, how DNA methylation is associated with high order chromatin structure is not clear. Currently, it is believed that the insulator protein CTCF binding is blocked by DNA methylation, occurring in its core binding site. Thus the disruption of CTCF binding will result in the ectopic assessment of enhancer in the isolated neighborhood. However, not all CTCF bears CpG sites in its core binding site and no integrated analysis has been applied to discover the relationship between DNA methylation and high order chromatin structure utilizing the DNA methylome data. Here we found the lowly methylated DNA methylation canyon are interacting with each other specifically in CD34+ CD38- hematopoietic stem and progenitor cells (HSPC) but not its differentiated progenitors. The DNA methylation canyon interactions are enriched for H3K27me3 mark and represent a different category of interactions other than looped domain mediated by CTCF extrusion mechanism. We also found these canyons are contributing to the active HOX gene expression acting as scaffolds for gene expression rather enhancers. Disruption of canyon interaction with CTCF deletion and whole canyon deletion result in a great compromise of self-renewal ability of HSPC and the decrease of expression of active HOXA/B gene.

ORGANISM(S): Homo sapiens

PROVIDER: GSE107024 | GEO | 2017/11/24

SECONDARY ACCESSION(S): PRJNA419390

REPOSITORIES: GEO

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