Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells
Abstract Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling...
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Nature Portfolio
2025-01-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55046-8 |
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| author | Yu Wang Jian Fan Xianbin Meng Qingyao Shu Yincui Wu Guo-Chao Chu Rong Ji Yinshan Ye Xiangwei Wu Jing Shi Haiteng Deng Lei Liu Yi-Ming Li |
| author_facet | Yu Wang Jian Fan Xianbin Meng Qingyao Shu Yincui Wu Guo-Chao Chu Rong Ji Yinshan Ye Xiangwei Wu Jing Shi Haiteng Deng Lei Liu Yi-Ming Li |
| author_sort | Yu Wang |
| collection | DOAJ |
| description | Abstract Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling in native cells remains challenging. Here, we develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells, by integrating cell-permeable and nuclear localization peptide modules into an hPTM peptide equipped with a photoreactive moiety. These types of probes, such as histone H3 lysine 4 trimethylation and histone H3 Lysine 9 crotonylation probes, enable the probing of epigenetic interactomes both in HeLa cell and hard-to-transfect RAW264.7 cells, resulting in the discovery of distinct interactors in different cell lines. The utility of this probe is further exemplified by characterizing interactome of emerging hPTM, such as AF9 was detected as a binder of histone H3 Lysine 9 lactylation, thus expanding the toolbox for profiling of hPTM-mediated PPIs in live cells. |
| format | Article |
| id | doaj-art-a297365fa9974d22b14a91b7270c1db4 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a297365fa9974d22b14a91b7270c1db42025-01-12T12:30:24ZengNature PortfolioNature Communications2041-17232025-01-0116111310.1038/s41467-024-55046-8Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cellsYu Wang0Jian Fan1Xianbin Meng2Qingyao Shu3Yincui Wu4Guo-Chao Chu5Rong Ji6Yinshan Ye7Xiangwei Wu8Jing Shi9Haiteng Deng10Lei Liu11Yi-Ming Li12School of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of TechnologyDepartment of Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of ChinaMOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua UniversityDepartment of Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of ChinaSchool of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of TechnologyNew Cornerstone Science Laboratory, Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua UniversitySchool of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of TechnologySchool of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of TechnologyNew Cornerstone Science Laboratory, Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua UniversityDepartment of Chemistry, Hefei National Laboratory of Physical Science at Microscale, University of Science and Technology of ChinaMOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua UniversityNew Cornerstone Science Laboratory, Tsinghua-Peking Center for Life Sciences, Ministry of Education Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Department of Chemistry, Tsinghua UniversitySchool of Food and Biological Engineering, Engineering Research Center of Bio-process, Ministry of Education, Key Laboratory of Animal Source of Anhui Province, Hefei University of TechnologyAbstract Dissection of the physiological interactomes of histone post-translational modifications (hPTMs) is crucial for understanding epigenetic regulatory pathways. Peptide- or protein-based histone photoaffinity tools expanded the ability to probe the epigenetic interactome, but in situ profiling in native cells remains challenging. Here, we develop a nucleus-targeting histone-tail-based photoaffinity probe capable of profiling the hPTM-mediated interactomes in native cells, by integrating cell-permeable and nuclear localization peptide modules into an hPTM peptide equipped with a photoreactive moiety. These types of probes, such as histone H3 lysine 4 trimethylation and histone H3 Lysine 9 crotonylation probes, enable the probing of epigenetic interactomes both in HeLa cell and hard-to-transfect RAW264.7 cells, resulting in the discovery of distinct interactors in different cell lines. The utility of this probe is further exemplified by characterizing interactome of emerging hPTM, such as AF9 was detected as a binder of histone H3 Lysine 9 lactylation, thus expanding the toolbox for profiling of hPTM-mediated PPIs in live cells.https://doi.org/10.1038/s41467-024-55046-8 |
| spellingShingle | Yu Wang Jian Fan Xianbin Meng Qingyao Shu Yincui Wu Guo-Chao Chu Rong Ji Yinshan Ye Xiangwei Wu Jing Shi Haiteng Deng Lei Liu Yi-Ming Li Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells Nature Communications |
| title | Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells |
| title_full | Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells |
| title_fullStr | Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells |
| title_full_unstemmed | Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells |
| title_short | Development of nucleus-targeted histone-tail-based photoaffinity probes to profile the epigenetic interactome in native cells |
| title_sort | development of nucleus targeted histone tail based photoaffinity probes to profile the epigenetic interactome in native cells |
| url | https://doi.org/10.1038/s41467-024-55046-8 |
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