Chromatin Remodeler Mutations in Human Cancers: Epigenetic Implications

Abstract

Chromatin remodeler complexes exhibit the ability to alter nucleosome composition and positions, with seemingly divergent roles in the regulation of chromatin architecture and gene expression. The outcome is directed by subunit variation and interactions with accessory factors. Recent studies have revealed that subunits of chromatin remodelers display an unexpectedly high mutation rate and/or are inactivated in a number of cancers. Consequently, a repertoire of epigenetic processes are likely to be affected, including interactions with histone modifying factors, as well as the ability to precisely modulate nucleosome positions, DNA methylation patterns and potentially, higher-order genome structure. However, the true significance of chromatin remodeler genetic aberrations in promoting a cascade of epigenetic changes, particularly during initiation and progression of cancer, remains largely unknown.

Keywords::

• ARID1A
• BRG1
• BRM
• cancer
• chromatin remodeling
• epigenetics
• nucleosome
• SNF5
• SWI/SNF

Financial & competing interests disclosure

We thank members of the Clark Epigenetics Laboratory for helpful discussions and careful reading of the manuscript and our funding sources. KA Skulte is supported by an Australian Postgraduate Award. PC Taberlay is a Cancer Institute NSW Early Career Development Fellow. This work was further supported by Cure Cancer Australia Foundation Project Grant #1060713 to P.C.T and NH & MRC Project Grant #1051757 to S.J.C and P.C.T. The authors have no other relevant affiliations, financial involvement or conflicts of interest with any organization other than those stated.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

We thank members of the Clark Epigenetics Laboratory for helpful discussions and careful reading of the manuscript and our funding sources. KA Skulte is supported by an Australian Postgraduate Award. PC Taberlay is a Cancer Institute NSW Early Career Development Fellow. This work was further supported by Cure Cancer Australia Foundation Project Grant #1060713 to P.C.T and NH & MRC Project Grant #1051757 to S.J.C and P.C.T. The authors have no other relevant affiliations, financial involvement or conflicts of interest with any organization other than those stated. No writing assistance was utilized in the production of this manuscript.