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© 2020. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Background: Histone post-translational modifications (PTMs) are involved in various biological processes such as transcriptional activation, chromosome packaging, and DNA repair. Previous studies mainly focused on PTMs by directly targeting histone-modifying enzymes such as HDACs and HATs.

Methods and Results: In this study, we discovered a previously unexplored regulation mechanism for histone PTMs by targeting transcription regulation factor 14-3-3ζ. Mechanistic studies revealed 14-3-3ζ dimerization as a key prerequisite, which could be dynamically induced via an allosteric effect. The selective inhibition of 14-3-3ζ dimer interaction with histone H3 modulated histone H3 PTMs by exposing specific modification sites including acetylation, trimethylation, and phosphorylation, and reprogrammed gene transcription profiles for autophagy-lysosome function and endoplasmic reticulum stress.

Conclusion: Our findings demonstrate the feasibility of editing histone PTM patterns by targeting transcription regulation factor 14-3-3ζ, and provide a distinctive PTM editing strategy which differs from current histone modification approaches.

Details

Title
Allosteric regulation of protein 14-3-3ζ scaffold by small-molecule editing modulates histone H3 post-translational modifications
Author
Yan-Jun, Wan; Li-Xi, Liao; Liu, Yang; Yang, Heng; Xiao-Min, Song; Li-Chao, Wang; Xiao-Wen, Zhang; Qian, Yi; Liu, Dan; Xiao-Meng, Shi; Li-Wen, Han; Xia, Qing; Ke-Chun, Liu; Zhi-Yong Du; Jiang, Yong; Ming-Bo Zhao; Ke-Wu, Zeng; Peng-Fei Tu
Pages
797-815
Section
Research Papers
Publication year
2020
Publication date
2020
Publisher
Ivyspring International Publisher Pty Ltd
e-ISSN
18387640
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2598257928
Copyright
© 2020. This work is published under https://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.