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

Martinez-Garcia, Eva, Popovic, Relja, Min, Dong-Joon, Sweet, Steve M M, Thomas, Paul M, Zamdborg, Leonid, Heffner, Aaron, Will, Christine, Lamy, Laurence, Staudt, Louis M, Levens, David L, Kelleher, Neil L and Licht, Jonathan D (2011) The MMSET histone methyl transferase switches global histone methylation and alters gene expression in t(4;14) multiple myeloma cells. Blood, 117 (1). pp. 211-220. ISSN 0006-4971

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Abstract

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.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science
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Depositing User: Steve Sweet
Date Deposited: 06 Feb 2012 18:52
Last Modified: 03 Apr 2013 11:42
URI: http://sro.sussex.ac.uk/id/eprint/18718
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