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Insights into histone code syntax from structural and biochemical studies of CARM1 methyltransferase

journal contribution
posted on 2023-06-08, 10:07 authored by Mark Roe, Markus Hassler, Laurence Pearl, Vivienne Thompson-Vale, Wyatt Yue
Coactivator-associated arginine methyltransferase (CARM1) is a transcriptional coactivator that methylates Arg17 and Arg26 in histone H3. CARM1 contains a conserved protein arginine methyltransferase (PRMT) catalytic core flanked by unique pre- and post-core regions. The crystal structures of the CARM1 catalytic core in the apo and holo states reveal cofactor-dependent formation of a substrate-binding groove providing a specific access channel for arginine to the active site. The groove is supported by the first eight residues of the post-core region (C-extension), not present in other PRMTs. In vitro methylation assays show that the C-extension is essential for all histone H3 methylation activity, whereas the pre-core region is required for methylation of Arg26, but not Arg17. Kinetic analysis shows Arg17 methylation is potentiated by pre-acetylation of Lys18, and this is reflected in kcat rather than Km. Together with the absence of specificity subsites in the structure, this suggests an electrostatic sensing mechanism for communicating the modification status of vicinal residues as part of the syntax of the 'histone code.'

History

Publication status

  • Published

Journal

EMBO Journal

ISSN

0261-4189

Publisher

Nature Publishing Group

Issue

20

Volume

26

Page range

4402-4412

Department affiliated with

  • Biochemistry Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

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