Joint profiling of chromatin accessibility and CRISPR edits via double-stranded DNA deaminases

joint-profiling-of-chromatin-accessibility-and-crispr-edits-via-double-stranded-dna-deaminases
Joint profiling of chromatin accessibility and CRISPR edits via double-stranded DNA deaminases
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Nature Methods (2025)Cite this article

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Targeted deaminase-accessible chromatin sequencing (TDAC-seq) measures chromatin accessibility across long chromatin fibers at targeted loci using double-stranded DNA cytidine deaminases. When combined with pooled CRISPR mutational screening, TDAC-seq enables the high-throughput detection of changes in chromatin accessibility following CRISPR perturbations, allowing fine mapping of sequence–function relationships within endogenous cis-regulatory elements.

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Fig. 1: TDAC-seq coupled with pooled CRISPR-mutational scanning.

References

  1. Canver, M. C. et al. BCL11A enhancer dissection by Cas9-mediated in situ saturating mutagenesis. Nature 527, 192–197 (2015). This paper describes CRISPR–Cas9 saturating mutagenesis of the BCL11A enhancer and validates it as a therapeutic target for fetal globin reinduction.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Sharma, A. et al. CRISPR-Cas9 editing of the HBG1 and HBG2 promoters to treat sickle cell disease. N. Engl. J. Med. 389, 820–832 (2023). This paper demonstrates that CRISPR–Cas9-mediated disruption of the HBG1 and HBG2 gene promoters is an effective therapeutic strategy for sickle cell disease.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Rubin, A. J. et al. Coupled single-cell CRISPR screening and epigenomic profiling reveals causal gene regulatory networks. Cell 176, 361–376.e17 (2019). This paper presents Perturb-ATAC, which measures CRISPR perturbations and genome-wide chromatin accessibility in single cells by detecting CRISPR guide RNAs rather than endogenous edits.

    Article  CAS  PubMed  Google Scholar 

  4. Stergachis, A. B., Debo, B. M., Haugen, E., Churchman, L. S. & Stamatoyannopoulos, J. A. Single-molecule regulatory architectures captured by chromatin fiber sequencing. Science 368, 1449–1454 (2020). This paper reports Fiber-seq, a long-read sequencing-based method for measuring chromatin accessibility using m6A methyltransferases.

    Article  CAS  PubMed  Google Scholar 

  5. Mok, B. Y. et al. A bacterial cytidine deaminase toxin enables CRISPR-free mitochondrial base editing. Nature 583, 631–637 (2020). This paper reports the first double-stranded DNA cytidine deaminase.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This is a summary of: Roh, H. et al. Coupling CRISPR scanning with targeted chromatin accessibility profiling using a double-stranded DNA deaminase. Nat. Methods https://doi.org/10.1038/s41592-025-02811-2 (2025).

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Joint profiling of chromatin accessibility and CRISPR edits via double-stranded DNA deaminases. Nat Methods (2025). https://doi.org/10.1038/s41592-025-02812-1

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  • DOI: https://doi.org/10.1038/s41592-025-02812-1