Journal article icon

Journal article

JmjC catalysed histone H2a N -methyl arginine demethylation and C4-arginine hydroxylation reveals importance of sequence-reactivity relationships

Abstract:
2-Oxoglutarate (2OG) dependent Nε-methyl lysine demethylases (JmjC-KDMs) regulate eukaryotic transcription. We report studies showing that isolated forms of all human KDM4 and KDM5 JmjC enzymes catalyse demethylation of N-methylated Arg-3 of histone H2a. Unexpectedly, the results reveal that KDM4E and, less efficiently, KDM4D catalyse C-4 hydroxylation of Arg-20 of H2a on peptides, recombinant H2a, and calf histone extracts, including when the Arg-20 guanidino group is N-methylated. Combined with previous observations, our biochemical results highlight the importance of sequence context in determining the relative efficiencies of lysine and arginine demethylation reactions catalysed by KDM4s and KDM5s. At least in some cases changes in sequence can also enable a different JmjC reaction mode, such as C-4 arginine hydroxylation instead of demethylation. Further work is thus required to define the full scope of JmjC catalysed reactions in cells.
Publication status:
Published
Peer review status:
Peer reviewed

Actions


Access Document


Files:
Publisher copy:
10.1038/s42003-024-07183-5

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemistry Research Laboratory
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemistry Research Laboratory
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemistry Research Laboratory
Role:
Author
ORCID:
0000-0001-7552-4966
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemistry Research Laboratory
Oxford college:
University College
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Chemistry
Sub department:
Chemistry Research Laboratory
Role:
Author


More from this funder
Funder identifier:
https://ror.org/0472cxd90
Programme:
H2020 Priority Excellent Science
More from this funder
Funder identifier:
https://ror.org/029chgv08


Publisher:
Springer Nature
Journal:
Communications Biology More from this journal
Volume:
7
Issue:
1
Article number:
1583
Publication date:
2024-11-27
Acceptance date:
2024-10-31
DOI:
EISSN:
2399-3642


Language:
English
Pubs id:
2067274
Local pid:
pubs:2067274
Source identifiers:
2453905
Deposit date:
2024-11-27

Terms of use



Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP