A CRISPR-Cas9 based shuffle system for endogenous histone H3 and H4 combinatorial mutagenesis

Abstract Post-translational modifications of histone proteins greatly impact gene expression and cell fate decisions in eukaryotes. To study these, it is important to develop a convenient, multiplex, and efficient method to precisely introduce mutations to histones. Because eukaryotic cells usually...

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Autores principales: Yu Fu, Zhenglin Zhu, Geng Meng, Rijun Zhang, Yueping Zhang
Formato: article
Lenguaje:EN
Publicado: Nature Portfolio 2021
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Acceso en línea:https://doaj.org/article/ffbb1424630d415db375e69bc16fdb70
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Sumario:Abstract Post-translational modifications of histone proteins greatly impact gene expression and cell fate decisions in eukaryotes. To study these, it is important to develop a convenient, multiplex, and efficient method to precisely introduce mutations to histones. Because eukaryotic cells usually contain multiple copies of histone genes, it is a challenge to mutate all histones at the same time by the traditional homologous recombination method. Here, we developed a CRISPR-Cas9 based shuffle system in Saccharomyces cerevisiae, to generate point mutations on both endogenous histone H3 and H4 genes in a rapid, seamless and multiplex fashion. Using this method, we generated yeast strains containing histone triple H3–K4R–K36R–K79R mutants and histone combinatorial H3–K56Q–H4–K59A double mutants with high efficiencies (70–80%). This CRISPR-Cas9 based mutagenesis system could be an invaluable tool to the epigenetics field.