
==== Front
bioRxiv
BIORXIV
bioRxiv
2692-8205
Cold Spring Harbor Laboratory

10.1101/2024.09.09.612085
preprint
1
Article
CRISPR-CLEAR: Nucleotide-Resolution Mapping of Regulatory Elements via Allelic Readout of Tiled Base Editing
Becerra Basheer
Wittibschlager Sandra
Patel Zain M.
Kutschat Ana P.
Delano Justin
Che Eric
Karjalainen Anzhelika
Wu Ting
Starrs Marlena
Jankowiak Martin
Bauer Daniel E.
Seruggia Davide
Pinello Luca http://orcid.org/0000-0003-1109-3823

09 9 2024
2024.09.09.612085https://creativecommons.org/licenses/by-nc-nd/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator.
http://biorxiv.org/lookup/doi/10.1101/2024.09.09.612085
nihpp-2024.09.09.612085.pdf
ABSTRACT

CRISPR tiling screens have advanced the identification and characterization of regulatory sequences but are limited by low resolution arising from the indirect readout of editing via guide RNA sequencing. This study introduces CRISPR-CLEAR , an end-to-end experimental assay and computational pipeline, which leverages targeted sequencing of CRISPR-introduced alleles at the endogenous target locus following dense base-editing mutagenesis. This approach enables the dissection of regulatory elements at nucleotide resolution, facilitating a direct assessment of genotype-phenotype effects.
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pmc
