PT  - JOURNAL ARTICLE
AU  - Jonathan Moody
AU  - Tsukasa Kouno
AU  - Akari Suzuki
AU  - Youtaro Shibayama
AU  - Chikashi Terao
AU  - Jen-Chien Chang
AU  - Fernando López-Redondo
AU  - Chi Wai Yip
AU  - Jessica Severin
AU  - Hiroyuki Suetsugu
AU  - Yoshinari Ando
AU  - Kazuhiko Yamamoto
AU  - Piero Carninci
AU  - Jay W. Shin
AU  - Chung-Chau Hon
TI  - Profiling of transcribed <em>cis</em>-regulatory elements in single cells
AID  - 10.1101/2021.04.04.438388
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.04.438388
4099  - http://biorxiv.org/content/early/2021/04/21/2021.04.04.438388.short
4100  - http://biorxiv.org/content/early/2021/04/21/2021.04.04.438388.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.