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bioRxiv · 10.1101/2021.04.04.438388

Profiling of transcribed cis-regulatory elements in single cells

Moody, J.·Kouno, T.·Suzuki, A.·Shibayama, Y.·Terao, C.·Chang, J.-C.·Lopez-Redondo, F.·Yip, C. W.·Ando, Y.·Yamamoto, K.·Carninci, P.·Shin, J. W.·Hon, C.-C.
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Abstract

Profiling of cis-regulatory elements (CREs, mostly promoters and enhancers) in single cells allows the interrogation of the cell-type and cell-state-specific contexts of gene regulation and genetic predisposition to diseases. Here we demonstrate single-cell RNA-5'end-sequencing (sc-end5-seq) methods can detect transcribed CREs (tCREs), enabling simultaneous quantification of gene expression and enhancer activities in a single assay at no extra cost. We showed enhancer RNAs can be detected using sc-end5-seq methods with either random or oligo(dT) priming. To analyze tCREs in single cells, we developed SCAFE (Single Cell Analysis of Five-prime Ends) to identify genuine tCREs and analyze their activities (https://github.com/chung-lab/scafe). As compared to accessible CRE (aCRE, based on chromatin accessibility), tCREs are more accurate in predicting CRE interactions by co-activity, more sensitive in detecting shifts in alternative promoter usage and more enriched in diseases heritability. Our results highlight additional dimensions within sc-end5-seq data which can be used for interrogating gene regulation and disease heritability.

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Moody, J., Kouno, T., Suzuki, A., Shibayama, Y., Terao, C., Chang, J.-C., Lopez-Redondo, F., Yip, C. W., Ando, Y., Yamamoto, K., Carninci, P., Shin, J. W., Hon, C.-C.. 2021-04-04. Profiling of transcribed cis-regulatory elements in single cells. https://doi.org/10.1101/2021.04.04.438388

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