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

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

PROVIDER: PRJNA743025 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR15014943_1.fastq.gz	Fastqsanger.gz
	SRR15014943_2.fastq.gz	Fastqsanger.gz
	SRR15014944_1.fastq.gz	Fastqsanger.gz
	SRR15014944_2.fastq.gz	Fastqsanger.gz
	SRR15014945_1.fastq.gz	Fastqsanger.gz

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

Project description: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 binding sites 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 showed similar enrichment patterns of histone modification to those observed in non-bisulfite-treated control; it further revealed that H3K4me1-marked regions are mostly CpG-poor, lack of 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 scenario with precious biological samples.

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CUT&Tag-BS for simultaneous profiling of histone modification and DNA methylation with high efficiency and low cost.

Project description: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 the 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 cleavage under targets and tagmentation (CUT&Tag) with tagmentation-based bisulfite sequencing (CUT&Tag-BS). We demonstrated the validity of our method using representative histone modifications of euchromatin and constitutive and facultative heterochromatin (H3K4me1, H3K9me3, and H3K27me3, respectively). Similar histone modification enrichment patterns were observed in CUT&Tag-BS compared with non-bisulfite-treated control, and H3K4me1-marked regions were found to mostly be CpG poor, lack methylation concordance, and exhibit prevalent DNA methylation heterogeneity among mouse embryonic stem cells (mESCs). 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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