Human transcription factor combinations mapped by genome-wide footprinting with deaminase

He, R.; Dong, W.; Ma, W.; Wang, Z.; Gao, L.; Xie, C.; Li, D.; Shen, K.; Jian, F.; Zhang, J.; Yuan, Y.; Wang, X.; Pang, Y.; Zhang, Z.; Zheng, Y.; Liu, S.; Luo, C.; Chai, X.; Ren, J.; Zhu, Z.; Xie, X. S.

doi:10.1101/2024.06.14.599019

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bioRxiv · 10.1101/2024.06.14.599019

Human transcription factor combinations mapped by genome-wide footprinting with deaminase

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Abstract

An individuals somatic cells have the same genome but exhibit cell-type-specific transcriptome regulated by a combination of transcription factors (TFs) for each gene. Mapping of TF sites on the human genome is critically important for understanding functional genomics. Here we report a novel technique to measure human TFs binding sites genome-wide with single-base resolution by footprinting with deaminase (FOODIE). Single-molecule sequencing reads from thousands of cells after in situ deamination yielded site-specific TF binding fractions and the cooperativity among adjacent TFs. In a human lymphoblastoid cell line, we found that genes in a correlated gene module (CGM) share TF(s) in their cis-regulatory elements to participate a particular biological function. Finally, single-cell resolved experiments (scFOODIE) allow cell-type-specific TF footprinting in heterogeneous brain tissues.

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He, R., Dong, W., Ma, W., Wang, Z., Gao, L., Xie, C., Li, D., Shen, K., Jian, F., Zhang, J., Yuan, Y., Wang, X., Pang, Y., Zhang, Z., Zheng, Y., Liu, S., Luo, C., Chai, X., Ren, J., Zhu, Z., Xie, X. S.. 2024-06-17. Human transcription factor combinations mapped by genome-wide footprinting with deaminase. https://doi.org/10.1101/2024.06.14.599019

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