Genome-wide single-cell and single-molecule footprinting of transcription factors with deaminase.

Autor:	He R; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China., Dong W; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; School of Life Sciences, Peking University, Beijing 100871, China., Wang Z; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; School of Life Sciences, Peking University, Beijing 100871, China., Xie C; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China., Gao L; Changping Laboratory, Beijing 102206, China., Ma W; Changping Laboratory, Beijing 102206, China., Shen K; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; School of Life Sciences, Peking University, Beijing 100871, China., Li D; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China., Pang Y; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China., Jian F; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China., Zhang J; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; School of Life Sciences, Peking University, Beijing 100871, China., Yuan Y; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China., Wang X; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China., Zhang Z; Changping Laboratory, Beijing 102206, China., Zheng Y; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China., Liu S; Changping Laboratory, Beijing 102206, China., Luo C; Academy for Advanced Interdisciplinary Studies, Peking University, Beijing 100871, China., Chai X; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China., Ren J; Changping Laboratory, Beijing 102206, China., Zhu Z; Changping Laboratory, Beijing 102206, China., Xie XS; Changping Laboratory, Beijing 102206, China.; Beijing Advanced Innovation Center for Genomics and Biomedical Pioneering Innovation Center, Peking University, Beijing 100871, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Dec 24; Vol. 121 (52), pp. e2423270121. Date of Electronic Publication: 2024 Dec 17.
DOI:	10.1073/pnas.2423270121
Abstrakt:	Decades of research have established that mammalian transcription factors (TFs) bind to each gene's regulatory regions and cooperatively control tissue specificity, timing, and intensity of gene transcription. Mapping the combination of TF binding sites genome wide is critically important for understanding functional genomics. Here, we report a technique to measure TFs' binding sites on the human genome with a near single-base resolution by footprinting with deaminase (FOODIE) on a single-molecule and single-cell basis. Single-molecule sequencing reads after enzymatic deamination allow detection of the TF binding fraction on a particular footprint and the binding cooperativity of any two adjacent TFs, which can be either positive or negative. As a newcomer of single-cell genomics, single-cell FOODIE enables the detection of cell-type-specific TF footprints in a pure cell population in a heterogeneous tissue, such as the brain. We found that genes carrying out a certain biological function together in a housing-keeping correlated gene module (CGM) or a tissues-specific CGM are coordinated by shared TFs in the gene's promoters and enhancers, respectively. Scalable and cost-effective, FOODIE allows us to create an open FOODIE database for cell lines, with applicability to human tissues and clinical samples. Competing Interests: Competing interests statement:R.H., W.D., Z.W., and X.S.X. are coinventors on patent application WO/2024/065721 that includes methods described in this manuscript. The remaining authors declare no competing interests.
Databáze:	MEDLINE
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