HMGN1 enhances CRISPR-directed dual-function A-to-G and C-to-G base editing

Chao Yang, Zhenzhen Ma, Keshan Wang, Xingxiao Dong, Meiyu Huang, Yaqiu Li, Xiagu Zhu, Ju Li, Zhihui Cheng, Changhao Bi () and Xueli Zhang ()
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Chao Yang: Chinese Academy of Sciences
Zhenzhen Ma: Nankai University
Keshan Wang: Huazhong University of Science and Technology
Xingxiao Dong: Dalian Polytechnic University
Meiyu Huang: Guangxi Normal University
Yaqiu Li: Chinese Academy of Sciences
Xiagu Zhu: Tianjin University of Science and Technology
Ju Li: Tianjin Normal University
Zhihui Cheng: Nankai University
Changhao Bi: Chinese Academy of Sciences
Xueli Zhang: Chinese Academy of Sciences

Nature Communications, 2023, vol. 14, issue 1, 1-12

Abstract: Abstract C-to-G base editors have been successfully constructed recently, but limited work has been done on concurrent C-to-G and A-to-G base editing. In addition, there is also limited data on how chromatin-associated factors affect the base editing. Here, we test a series of chromatin-associated factors, and chromosomal protein HMGN1 was found to enhance the efficiency of both C-to-G and A-to-G base editing. By fusing HMGN1, GBE and ABE to Cas9, we develop a CRISPR-based dual-function A-to-G and C-to-G base editor (GGBE) which is capable of converting simultaneous A and C to G conversion with substantial editing efficiency. Accordingly, the HMGN1 role shown in this work and the resulting GGBE tool further broaden the genome manipulation capacity of CRISPR-directed base editors.

Date: 2023
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DOI: 10.1038/s41467-023-38193-2

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