open access publication

Article, 2024

Spatial chromatin accessibility sequencing resolves high-order spatial interactions of epigenomic markers

ELIFE, ISSN 2050-084X, 2050-084X, Volume 12, 10.7554/eLife.87868

Contributors

Xie, YM [1] Ruan, Feng [1] Li, Yaning 0000-0001-9563-9330 [1] Luo, Meng 0000-0002-4650-7996 [1] Zhang, Chen [1] Chen, Zhichao 0000-0002-7297-5064 [1] [2] [3] Xie, Zhe 0000-0003-0311-6781 [2] [3] [4] Weng, Zhe [1] Chen, Weitian [1] [2] [3] Chen, Wenfang [1] Fang, Yi Tong 0000-0001-7255-0958 [1] Lad, N. N. 0000-0001-7801-4689 [1] Guo, Mei [1] Wang, Juan [1] Xu, Shouping [5] wang, hongqi (Corresponding author) [1] Tang, Chong (Corresponding author) [1]

Affiliations

  1. [1] BGI Shenzhen, BGI Genom, Shenzhen, Peoples R China
  2. [NORA names: China; Asia, East];
  3. [2] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
  4. [NORA names: China; Asia, East];
  5. [3] Univ Chinese Acad Sci, Coll Life Sci, Beijing, Peoples R China
  6. [NORA names: China; Asia, East];
  7. [4] Univ Copenhagen, Dept Biol Cell Biol & Physiol, Copenhagen, Denmark
  8. [NORA names: KU University of Copenhagen; University; Denmark; Europe, EU; Nordic; OECD];
  9. [5] Harbin Med Univ, Canc Hosp, Dept Breast Surg, Harbin, Peoples R China
  10. [NORA names: China; Asia, East]

Abstract

As the genome is organized into a three-dimensional structure in intracellular space, epigenomic information also has a complex spatial arrangement. However, most epigenetic studies describe locations of methylation marks, chromatin accessibility regions, and histone modifications in the horizontal dimension. Proper spatial epigenomic information has rarely been obtained. In this study, we designed spatial chromatin accessibility sequencing (SCA-seq) to resolve the genome conformation by capturing the epigenetic information in single-molecular resolution while simultaneously resolving the genome conformation. Using SCA-seq, we are able to examine the spatial interaction of chromatin accessibility (e.g. enhancer-promoter contacts), CpG island methylation, and spatial insulating functions of the CCCTC-binding factor. We demonstrate that SCA-seq paves the way to explore the mechanism of epigenetic interactions and extends our knowledge in 3D packaging of DNA in the nucleus.

Keywords

3D genome, DNA methylation, GpC methyltransferase, Hi-C, Human, chromatin accessibility, pore-C

Data Provider: Clarivate