Tudor domain of histone demethylase KDM4B is a reader of H4K20me3.

Abstract

The lysine histone demethylase KDM4B is overexpressed in several types of cancers and plays dual roles in genome stability maintenance. Although KDM4B is able to recognize several histone methylations, the underlying molecular mechanism is still unknown. In this study, we purified the KDM4B chromatin-associated hybrid tudor domains (HTDs) and plant home domains (PHDs) and performed the pull-down assay to screen the tri-methyl modified histone peptides that could be efficiently recognized by KDM4B. Our results showed that both HTD alone and the combination of HTD and PHD were able to specifically bind to H3K4me3 and H4K20me3. Because H4K20me3 is essential for KDM4B's rapid recruitment to DNA damage site, we further aligned the multiple tudor peptide sequence and identified two conserved residues Y993 and W987 that are critical for KDM4B-H4K20me3 interaction. The surface plasmon resonance analysis revealed that HTD displayed a rapid H4K20me3 bind-dissociate pattern. These findings therefore provided mechanistic insights into the binding of tudor domain of KDM4B protein with H4K20me3.

• Authors: Ying Xiang, Jing Guo, Feng Li, Jie Xiong
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 52 Issue 8 Pg. 901-906 (Aug 05 2020) ISSN: 1745-7270 [Electronic] China
• PMID: 32537648 (Publication Type: Journal Article)
• Copyright: © The Author(s) 2020. Published by Oxford University Press on behalf of the Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Histones
• Jumonji Domain-Containing Histone Demethylases
• KDM4B protein, human

Topics

• Cell Line
• Histones (chemistry, metabolism)
• Humans
• Jumonji Domain-Containing Histone Demethylases (chemistry, metabolism)
• Protein Binding
• Protein Domains
• Surface Plasmon Resonance