RRC ID 58053
Author Lee DS, Luo C, Zhou J, Chandran S, Rivkin A, Bartlett A, Nery JR, Fitzpatrick C, O'Connor C, Dixon JR, Ecker JR.
Title Simultaneous profiling of 3D genome structure and DNA methylation in single human cells.
Journal Nat Methods
Abstract Dynamic three-dimensional chromatin conformation is a critical mechanism for gene regulation during development and disease. Despite this, profiling of three-dimensional genome structure from complex tissues with cell-type specific resolution remains challenging. Recent efforts have demonstrated that cell-type specific epigenomic features can be resolved in complex tissues using single-cell assays. However, it remains unclear whether single-cell chromatin conformation capture (3C) or Hi-C profiles can effectively identify cell types and reconstruct cell-type specific chromatin conformation maps. To address these challenges, we have developed single-nucleus methyl-3C sequencing to capture chromatin organization and DNA methylation information and robustly separate heterogeneous cell types. Applying this method to >4,200 single human brain prefrontal cortex cells, we reconstruct cell-type specific chromatin conformation maps from 14 cortical cell types. These datasets reveal the genome-wide association between cell-type specific chromatin conformation and differential DNA methylation, suggesting pervasive interactions between epigenetic processes regulating gene expression.
Volume 16(10)
Pages 999-1006
Published 2019-10-1
DOI 10.1038/s41592-019-0547-z
PII 10.1038/s41592-019-0547-z
PMID 31501549
PMC PMC6765423
MeSH Algorithms Chromatin / metabolism DNA Methylation* Datasets as Topic Epigenesis, Genetic Gene Expression Regulation Genome, Human* Genome-Wide Association Study Humans Single-Cell Analysis*
IF 30.822
Times Cited 7
Resource
Human and Animal Cells NMuMG/Fucci2(RCB2868)