Inhibition of a K9/K36 demethylase by an H3.3 point mutation found in paediatric glioblastoma

Hsiao P. J. Voon, Maheshi Udugama, Wendi Lin, Linda Hii, Ruby H.P. Law, David L. Steer, Partha P. Das, Jeffrey R. Mann and Lee H. Wong ()
Additional contact information
Hsiao P. J. Voon: Monash University
Maheshi Udugama: Monash University
Wendi Lin: Monash University
Linda Hii: Monash University
Ruby H.P. Law: Monash University
David L. Steer: Monash University
Partha P. Das: Monash University
Jeffrey R. Mann: Monash University
Lee H. Wong: Monash University

Nature Communications, 2018, vol. 9, issue 1, 1-10

Abstract: Abstract An array of oncogenic histone point mutations have been identified across a number of different cancer studies. It has been suggested that some of these mutant histones can exert their effects by inhibiting epigenetic writers. Here, we report that the H3.3 G34R (glycine to arginine) substitution mutation, found in paediatric gliomas, causes widespread changes in H3K9me3 and H3K36me3 by interfering with the KDM4 family of K9/K36 demethylases. Expression of a targeted single-copy of H3.3 G34R at endogenous levels induced chromatin alterations that were comparable to a KDM4 A/B/C triple-knockout. We find that H3.3 G34R preferentially binds KDM4 while simultaneously inhibiting its enzymatic activity, demonstrating that histone mutations can act through inhibition of epigenetic erasers. These results suggest that histone point mutations can exert their effects through interactions with a range of epigenetic readers, writers and erasers.

Date: 2018
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-018-05607-5 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-05607-5

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-018-05607-5

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().