Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.

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Publication Details

Journal
Protein & Cell
Published
2025-08-03
DOI
https://doi.org/10.1093/procel/pwaf071
Citations
1
Primary Topic
RNA modifications and cancer
Type
article
Field-Weighted Citation Impact
0.81
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article

Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq

Xiyang Chen, Juan Tang, Lan Kang, Bin He et al.
1 citations
Protein & Cell
RNA modifications and cancer
0.81
article

Genome-wide investigation of transcription factor footprints and dynamics using cFOOT-seq

Xiyang Chen, Juan Tang, Lan Kang, Bin He, Shan Bian, Jiejun Shi, Shaorong Gao, Chenfei Wang, Zhihua Shi, Jianhuang Xue, Yiqun Zhang, Kun Chen, Heng Wang, Xiaoyu Liu, Yihan Li, Xiaosong Wang, Jiamin Zhang, Mengchen Yang, Xiaofang Cheng, Yujun Hou, Kai Chen, Di Zhou, Yutao Fu, Ang Wu
article en
1 citations

Abstract

Gene regulation relies on the precise binding of transcription factors (TFs) at regulatory elements, but simultaneously detecting hundreds of TFs on chromatin is challenging. We developed cFOOT-seq, a cytosine deaminase-based TF footprinting assay, for high-resolution, quantitative genome-wide assessment of TF binding in both open and closed chromatin regions, even with small cell numbers. By utilizing the dsDNA deaminase SsdAtox, cFOOT-seq converts accessible cytosines to uracil while preserving genomic integrity, making it compatible with techniques like ATAC-seq for sensitive and cost-effective detection of TF occupancy at the single-molecule and single-cell level. Our approach enables the delineation of TF footprints, quantification of occupancy, and examination of chromatin influences on TF binding. Notably, cFOOT-seq, combined with FootTrack analysis, enables de novo prediction of TF binding sites and tracking of TF occupancy dynamics. We demonstrate its application in capturing cell type-specific TFs, analyzing TF dynamics during reprogramming, and revealing TF dependencies on chromatin remodelers. Overall, cFOOT-seq represents a robust approach for investigating the genome-wide dynamics of TF occupancy and elucidating the cis-regulatory architecture underlying gene regulation.

Protein & CellVol. 16(11)
Tongji University (CN), Shanghai First Maternity and Infant Hospital (CN)
Openalex Percentile: Top 25%
RNA modifications and cancer
0.81
DOIOpen Access PDFOpenAlex
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