Joint profiling of DNA methylation and chromatin architecture in single cells

Abstract

We report a method, Methyl-HiC, which captures the chromosome conformation and DNA methylome together in a cell. We use it to reveal coordinated DNA methylation status between distal genomic segments that are in spatial proximity in the nucleus and delineate heterogeneity of both the chromatin architecture and DNA methylome in a mixed population. Methyl-HiC enables simultaneous characterization of cell-type specific chromatin organization and epigenome in complex tissues. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

cfNOMe — A single assay for comprehensive epigenetic analyses of cell-free DNA

“…This method targets open chromatin, however, and is therefore not applicable to cfDNA. Other methods of jointly profiling independent epigenetic attributes (methylation and chromatin conformation) in nuclear DNA have also recently been described [17].…”

Multiomics analysis reveals extensive epigenome remodeling during cortical development

“…Our immuno-FACS approach allowed us to combine the resolution and depth of bulk Hi-C/DNA methylation with cell-type-specificity. The reduced input requirements and the improved resolution compared to prior studies (Lee et al, 2019;Li et al, 2019) enable the application of this method to other tissues and model organisms, where high-quality antibodies exist.…”

“…Methyl-Hi-C For Methyl-Hi-C we adapted current protocols (Lee et al, 2019;Li et al, 2019). Briefly, frozen pellets of fixed cells were thawed on ice, lysed with 0.2% Igepal-CA630 (Sigma-Aldrich, Cat.…”

“…To obtain a more comprehensive view of how chromatin landscape is reorganized during neural differentiation, we decided to employ a bulk approach using scRNA-based markers to sort precise cell populations, followed by combined mapping of 3D genome architecture and DNA methylation. Our method is based on the recently described methyl Hi-C protocols (Lee et al, 2019;Li et al, 2019), with the following improvements: 1) enrichment of desired cell types by immunoFACS; 2) significantly reduced input requirements (100-200k cells) and 3) higher proportion of Hi-C contacts/unique reads (Methods).…”

The impact factors of 3D genome organization

“…而这些不同甲基化模式与三维 基因组结构的具体关系也引起研究人员的兴趣. 随着 单细胞测序技术的不断进步, 研究人员开发出了在单 细胞水平同时测定全基因组DNA甲基化水平和染色 质三维结构的方法 [81,82] , 这使得DNA甲基化与三维基 [86] . 对与RNA聚合酶Ⅱ相关 的全基因组染色质相互作用进行分析发现, 在RNA聚 合酶Ⅱ结合位点中, 有65%与染色质相互作用有关, 这 意味着RNA聚合酶Ⅱ与染色质环的形成有关 [42] .…”