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<p>Mapping of protein-DNA interactions at single-cell resolution remains a central challenge in epigenomics, particularly for transcription factors&#xa0;(TFs), whose sparse binding limits reliable detection. Here, we establish DeChIC-seq (DNA Deaminase-based Chromatin Immuno-Conversion sequencing), a conversion-based strategy that uses a protein&#xa0;A-DddA<sub>tox</sub> fusion to directly record protein-DNA interactions by inducing localized C-to-U conversions near antibody-bound chromatin. Retaining genome-wide background sequence information without immunoprecipitation, DeChIC-seq enables profiling of histone modifications and sensitive detection of TF binding. Integration with single-cell whole-genome amplification extends DeChIC-seq to single-cell applications (scDeChIC-seq), enabling chromatin profiling of individual cells. Applied to mouse embryogenesis, scDeChIC-seq resolves lineage-specific chromatin states through profiling of H3K4me3, CTCF, and RAD21 and sensitively detects TF binding, including that of NR5A2, TFAP2C, and KLF5, from extremely limited blastomere inputs. This underscores its strong potential for detecting TF-binding sites in scarce biological samples. DeChIC-seq establishes a conversion-based framework for chromatin profiling that enables mechanistic dissection of TF-driven gene regulation across rare cells, developmental systems, and disease contexts.</p>

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Genome-wide profiling of histone modifications and transcription factor binding at single-cell resolution by DeChIC-seq

  • 期刊论文

  • 发表日期：

    2026年7月13日

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  • Zhifei Shi,
  • Xiyang Chen,
  • Yijia Yang,
  • Ang Wu,
  • Heng Wang,
  • Kai Chen,
  • Chong Li,
  • Lina Zou,
  • Zhipeng Qu,
  • Yuyan Zhao,
  • Wenjing Gan,
  • Shuhui Li,
  • Jiayu Chen,
  • Wenqiang Liu,
  • Jiejun Shi,
  • Hong Wang,
  • Jia-min Zhang,
  • Chenfei Wang,
  • Shaorong Gao,
  • Xiaoyu Liu

摘要

Mapping of protein-DNA interactions at single-cell resolution remains a central challenge in epigenomics, particularly for transcription factors (TFs), whose sparse binding limits reliable detection. Here, we establish DeChIC-seq (DNA Deaminase-based Chromatin Immuno-Conversion sequencing), a conversion-based strategy that uses a protein A-DddAtox fusion to directly record protein-DNA interactions by inducing localized C-to-U conversions near antibody-bound chromatin. Retaining genome-wide background sequence information without immunoprecipitation, DeChIC-seq enables profiling of histone modifications and sensitive detection of TF binding. Integration with single-cell whole-genome amplification extends DeChIC-seq to single-cell applications (scDeChIC-seq), enabling chromatin profiling of individual cells. Applied to mouse embryogenesis, scDeChIC-seq resolves lineage-specific chromatin states through profiling of H3K4me3, CTCF, and RAD21 and sensitively detects TF binding, including that of NR5A2, TFAP2C, and KLF5, from extremely limited blastomere inputs. This underscores its strong potential for detecting TF-binding sites in scarce biological samples. DeChIC-seq establishes a conversion-based framework for chromatin profiling that enables mechanistic dissection of TF-driven gene regulation across rare cells, developmental systems, and disease contexts.