SWI/SNF complexes and cancers

Abstract

Epigenetics refers to the study of genetic changes that can affect gene expression without altering the underlying DNA sequence, including DNA methylation, histone modification, chromatin remodelling, X chromosome inactivation and non-coding RNA regulation. Of these, DNA methylation, histone modification and chromatin remodelling constitute the three classical modes of epigenetic regulation. These three mechanisms alter gene transcription by adjusting chromatin accessibility, thereby affecting cell and tissue phenotypes in the absence of DNA sequence changes. In the presence of ATP hydrolases, chromatin remodelling alters the structure of chromatin and thus changes the transcription level of DNA-guided RNA. To date, four types of ATP-dependent chromatin remodelling complexes have been identified in humans, namely SWI/SNF, ISWI, INO80 and NURD/MI2/CHD. SWI/SNF mutations are prevalent in a wide variety of cancerous tissues and cancer-derived cell lines as discovered by next-generation sequencing technologies. SWI/SNF can bind to nucleosomes and use the energy of ATP to disrupt DNA and histone interactions, sliding or ejecting histones, altering nucleosome structure, and changing transcriptional and regulatory mechanisms. Furthermore, mutations in the SWI/SNF complex have been observed in approximately 20 % of all cancers. Together, these findings suggest that mutations targeting the SWI/SNF complex may have a positive impact on tumorigenesis and cancer progression.

Keywords: Cancers; SWI/SNF complexes; Structure and biochemistry; Subunit mutant.