CHEMICAL SCIENCE

Studies have found functional differences in different histone acylation modifications


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Screenshot of the paper

On May 30, Beijing time, the cooperation results of Luo Xiaozhou’s research group at the Institute of Synthetic Biology of the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, and the Liu Tao research group and Liu Xiaoyun research group of Peking University were published in the internationally renowned academic journal “German Applied Chemistry”, and the research team created a strain of Saccharomyces cerevisiae containing co-translational modification (CTM) nucleosomes based on gene codon extension technology. Further reveals biological functional differences in different types of histone acylation modifications in eukaryotes.

Zhao Yingming’s research group first reported the existence of crotonylation modification in Cell magazine in 2011, and in the decades since, this modification has become a research hotspot in the field of eukaryote post-translational modification. Crotonylation modification is closely related to acetylation modification because the modification as a marker for gene transcriptional activation, similar to acetylation modification, is a modification process in which enzymes are involved in regulation, and the two have a common modification/demodeling enzyme to some extent. However, studies have shown that crotonylation modifications may have biological functions that differ from acetylation modifications and have not yet been discovered. Lacking research tools to introduce different acylation modifications at specific sites of histones, the researchers set their sights on gene codon extension technology, which encodes non-classical amino acids with specific acylation modifications (i.e., CTM amino acids) to specific sites of the host protein through aminoacyl tRNA synthase/tRNA pairs that are orthogonal to the host organism.

First, the researchers screened and optimized the codon extension system with high insertion efficiency and orthogon, and verified the feasibility of the method on enhanced green fluorescent protein. The researchers then used Saccharomyces cerevisiae as a model organism to modify its genome to obtain a yeast containing CTM nucleosomes (pM56), which knocks out the wild-type histone H3 encoded by the genome and expresses the CTM histone H3 mutant. Histone H3 mutants can be obtained by performing non-classical amino acid mutations at their 56 sites with the help of the Saccharomyces cerevisiae gene codon extension system. Eventually, the researchers used the technique to introduce acetylation and crotonylation modifications at site 56 of yeast histone H3. The researchers found that the acetylation co-modification of histone H3K56 at the site of histone H3K56 in this strain provided a more favorable chromatin environment for DNA damage repair in Saccharomyces cerevisiae, and there were also differences in the effect of the two on the abundance of post-translational modifications at other sites.

Through interdisciplinary collaboration in chemical biology, synthetic biology and bioinformatics, based on the codon extension system of Saccharomyces cerevisiae, this study exploratorily uses fixed-point co-translation modification as a research method for synthetic epigenetics, creating another possible life form, that is, maintaining the life form of yeast life activity by artificially introducing co-translational modified amino acids. This particular organism not only provides more possibilities for exploring the intricate biological functions of post-translational modification of eukaryotic histones, but also provides new ideas and perspectives for studying the evolution of the role of post-translational modifications in the long process of evolution.

Liu Tao, a researcher at the School of Pharmacy of Peking University, Luo Xiaozhou, a researcher at the Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, and Liu Xiaoyun, a researcher at the School of Basic Medical Sciences of Peking University, are co-corresponding authors. Wu Dan, a master’s student from Peking University, Chen Xiaoxu, a postdoctoral fellow (now a postdoctoral fellow at Northwestern Polytechnical University), Zhang Yunfeng, assistant researcher at the Shenzhen Institute of Advanced Technology of the Chinese Academy of Sciences, and Tang Zhiheng, a doctoral student at Peking University, are the co-first authors of the paper. (Source: China Science Daily Diao Wenhui)

Related paper information:https://doi.org/10.1002/anie.202205570



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