University of Sussex
Browse

File(s) not publicly available

The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells

journal contribution
posted on 2023-06-07, 21:37 authored by Eva Martinez-Garcia, Relja Popovic, Dong-Joon Min, Steve M M Sweet, Paul M Thomas, Leonid Zamdborg, Aaron Heffner, Christine Will, Laurence Lamy, Louis M Staudt, David L Levens, Neil L Kelleher, Jonathan D Licht
The multiple myeloma SET domain (MMSET) protein is overexpressed in multiple myeloma (MM) patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/Wolf-Hirschhorn syndrome candidate 1 in development, its mode of action in the pathogenesis of MM is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth, and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation, and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.

History

Publication status

  • Published

Journal

Blood

ISSN

0006-4971

Publisher

American Society of Hematology

Issue

1

Volume

117

Page range

211-220

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • No

Peer reviewed?

  • Yes

Legacy Posted Date

2012-02-06

Usage metrics

    University of Sussex (Publications)

    Categories

    No categories selected

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC