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  3. High-throughput capture of actively transcribed region-interacting sequences reveals an intricate promoter-centered regulatory network

High-throughput capture of actively transcribed region-interacting sequences reveals an intricate promoter-centered regulatory network

  • Mol Cell. 2025 Dec 4;85(23):4463-4479.e7. doi: 10.1016/j.molcel.2025.10.018.
Xinxin Li 1,  Jinsheng Xu 2,  Xiaohao Yan 3,  Jiayong Zhong 4,  Chunhui Hou 5,  Chuanle Xiao 6,  Longjian Niu 7,  Wei Chi 8
Affiliations

Affiliations

  • 1 School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China.
  • 2 State Key Laboratory of Genetic Evolution & Animal Models, Yunnan Key Laboratory of Biodiversity Information, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China.
  • 3 Department of Biology, Southern University of Science and Technology, Shenzhen 518055, China.
  • 4 Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, 18 Zetian Road, Futian District, Shenzhen 518040, China.
  • 5 State Key Laboratory of Genetic Evolution & Animal Models, Yunnan Key Laboratory of Biodiversity Information, KIZ-CUHK Joint Laboratory of Bioresources and Molecular Research in Common Diseases, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming 650201, China. Electronic address: [email protected].
  • 6 State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Guangzhou 510060, China. Electronic address: [email protected].
  • 7 Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, 18 Zetian Road, Futian District, Shenzhen 518040, China; School of Public Health and Emergency Management, Southern University of Science and Technology, Shenzhen 518055, China. Electronic address: [email protected].
  • 8 Shenzhen Eye Hospital, Shenzhen Eye Medical Center, Southern Medical University, 18 Zetian Road, Futian District, Shenzhen 518040, China. Electronic address: [email protected].
PMID: 41260212 DOI: 10.1016/j.molcel.2025.10.018
Abstract

Understanding the intricate relationship between three-dimensional chromatin structure and gene expression regulation is essential for cellular biology. However, current techniques are insufficient to capture regulatory elements functioning through three-dimensional chromatin structures. Here, we present high-throughput capture of actively transcribed region-interacting sequences (Hi-Coatis), a high-throughput method that seamlessly integrates the detection of active transcription signals with three-dimensional chromatin interaction studies. Hi-Coatis operates without antibodies or probes, enabling low-input cell experiments with high resolution and robustness, capturing more than 93% of expressed genes and over 60,000 regulatory loci in human cells. The repetitive/copy number variation (CNV) regions and the promoter regions of C2 genes, defined by the distribution patterns of Hi-Coatis signals, both exhibit strong regulatory element activity. Notably, in the Hemin-induced erythroid differentiation model of K562 cells, Hi-Coatis uncovers the potential for silent genes to transition to transcriptionally active states through the cooperative influence of specific transcription factors (e.g., CCCTC-binding factor [CTCF] and cohesin complex subunits Rad21 [RAD21]) and regulatory elements.

Keywords

3D chromatin interactions; Hi-Coatis; actively transcribed regions; gene regulation; regulatory elements; repetitive genomic elements.

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