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bioRxiv · 10.1101/2021.07.19.452967

CUT&Tag-BS: an efficient and low-cost method for simultaneous profiling of histone modification and DNA methylation

Li, R.·Grimm, S. A.·Wade, P.
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Abstract

It remains a challenge to decipher the complex relationship between DNA methylation, histone modification, and the underlying DNA sequence with limited input material. Here, we developed an efficient, low-input, and low-cost method for simultaneous profiling of genomic localization of histone modification and methylation status of the underlying DNA at single-base resolution from the same cells in a single experiment by integrating CUT&Tag with tagmentation-based bisulfite sequencing (CUT&Tag-BS). We demonstrated the validity of our method for both active and repressive histone modifications using 250,000 mouse ESCs. CUT&Tag-BS shows similar enrichment patterns of histone modification to those observed in non-bisulfite-treated control; it further reveals that H3K4me1-marked regions are mostly CpG-poor, lack methylation concordance, and exhibit prevalent DNA methylation heterogeneity among the cells. We anticipate that CUT&Tag-BS will be widely applied to directly address the genomic relationship between DNA methylation and histone modification, especially in low-input scenarios with precious biological samples.

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Li, R., Grimm, S. A., Wade, P.. 2021-07-20. CUT&Tag-BS: an efficient and low-cost method for simultaneous profiling of histone modification and DNA methylation. https://doi.org/10.1101/2021.07.19.452967

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