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Characterization of the histone methyltransferase PRDM9 using biochemical, biophysical and chemical biology techniques

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posted on 2023-06-09, 19:35 authored by Xiaoying Koh-Stenta, Joma Joy, Anders Poulsen, Rong Li, Yvonne Tan, Yoonjung Shim, Jung-Hyun Min, Liling Wu, Anna Ngo, Jianhe Peng, Wei Guang Seetoh, Jing Cao, John Liang Kuan Wee, Perlyn Zekui Kwek, Alvin Hung, Umayal Lakshmanan, Horst Flotow, Ernesto Guccione, Jeffrey Hill
PRDM proteins have emerged as important regulators of disease and developmental processes. To gain insight into the mechanistic actions of the PRDM family, we have performed comprehensive characterization of a prototype member protein, the histone methyltransferase PRDM9, using biochemical, biophysical and chemical biology techniques. In the present paper we report the first known molecular characterization of a PRDM9-methylated recombinant histone octamer and the identification of new histone substrates for the enzyme. A single C321P mutant of the PR/SET domain was demonstrated to significantly weaken PRDM9 activity. Additionally, we have optimized a robust biochemical assay amenable to high-throughput screening to facilitate the generation of small-molecule chemical probes for this protein family. The present study has provided valuable insight into the enzymology of an intrinsically active PRDM protein.

History

Publication status

  • Published

File Version

  • Accepted version

Journal

Biochemical Journal

ISSN

0264-6021

Publisher

Portland Press

Issue

2

Volume

461

Page range

323-334

Department affiliated with

  • Biochemistry Publications

Research groups affiliated with

  • Sussex Drug Discovery Centre Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2019-11-11

First Open Access (FOA) Date

2019-11-11

First Compliant Deposit (FCD) Date

2019-11-11

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