Nature Communications (Apr 2023)

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,
  • Xueli Zhang

DOI
https://doi.org/10.1038/s41467-023-38193-2
Journal volume & issue
Vol. 14, no. 1
pp. 1 – 12

Abstract

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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.