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Nat Methods. 2019 Oct;16(10):999-1006. doi: 10.1038/s41592-019-0547-z. Epub 2019 Sep 9.

Simultaneous profiling of 3D genome structure and DNA methylation in single human cells.

Author information

1
Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
2
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA.
3
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA.
4
Flow Cytometry Core Facility, The Salk Institute for Biological Studies, La Jolla, CA, USA.
5
Peptide Biology Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA. jedixon@salk.edu.
6
Genomic Analysis Laboratory, The Salk Institute for Biological Studies, La Jolla, CA, USA. ecker@salk.edu.
7
Howard Hughes Medical Institute, The Salk Institute for Biological Studies, La Jolla, CA, USA. ecker@salk.edu.

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.

PMID:
31501549
PMCID:
PMC6765423
[Available on 2020-03-09]
DOI:
10.1038/s41592-019-0547-z

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