2. Academic Validation
  3. IT-scC&T-seq streamlines scalable, parallel profiling of protein-DNA interactions in single cells

IT-scC&T-seq streamlines scalable, parallel profiling of protein-DNA interactions in single cells

  • Genome Biol. 2025 Jul 7;26(1):196. doi: 10.1186/s13059-025-03661-z.
Jingchun Ma # 1,  Wei Jin # 2 3,  Li Rong # 1,  Zhanyu Gao 1,  Zaman Hazrat 1,  Hosen Md Shakhawat 1,  Fei Long 1,  Zixuan Zhang 1,  Jiandong Huang 1,  Xiaomei Lu 4,  Guoxiang Jin 5,  Zhongjun Zhou 6 7 8 9
Affiliations

Affiliations

  • 1 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China.
  • 2 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. jinwei5@connect.hku.hk.
  • 3 Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan, China. jinwei5@connect.hku.hk.
  • 4 Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan, China.
  • 5 Medical Research Centre, Guangdong Key Laboratory for Immune and Genetic Research of Chronic Nephropathy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
  • 6 School of Biomedical Sciences, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China. zhongjun@hku.hk.
  • 7 Dongguan Institute of Pediatrics, Dongguan Children's Hospital, Dongguan, China. zhongjun@hku.hk.
  • 8 Medical Research Centre, Guangdong Key Laboratory for Immune and Genetic Research of Chronic Nephropathy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China. zhongjun@hku.hk.
  • 9 Department of Orthopaedics and Traumatology, The University of Hong Kong Shenzhen Hospital, Shenzhen, China. zhongjun@hku.hk.
  • # Contributed equally.
PMID: 40624534 DOI: 10.1186/s13059-025-03661-z
Abstract

Single-cell profiling protein-chromatin interactions is often constrained by complex workflows, high cost, or dependence on specialized equipment. We present indexed tagmentation-based single-cell CUT&Tag-sequencing (IT-scC&T-seq), a modular, plate-based strategy using three-round combinatorial barcoding. IT-scC&T-seq robustly profiles histone modifications and transcription factors with high specificity and throughput, supporting simultaneous analysis of multiple samples and epitopes. Notably, it enables sensitive single-cell mapping of lamina-associated domains, low-abundance chromatin features previously difficult to resolve. Applied to adult mouse mammary gland, the method reveals cell-type-specific chromatin landscapes and lineage-regulatory dynamics. Together, IT-scC&T-seq provides a scalable, cost-effective, and broadly accessible approach for high-resolution chromatin profiling.

Keywords

CUT&Tag; Epigenetics; Histone modification; Indexed tagmentation; Lamina-associated domains (LADs); Mammary gland development; Single-cell omics.

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