title: LINE-1 activation and epigenetic silencing of suppressor genes in cancer: Causally related events?
abstract: The ability of active retrotransposon elements to move within the host genome and alter gene expression with subsequent phenotypic variation led to their initial discovery. In recent years it has become apparent that these elements can also modulate host gene expression independently of their transposition activity. Many retrotransposons maintain endogenous promoter motifs that can potentially drive expression of adjacent DNA modules. Similarly to transposition dependent dysregulation, these proto-promoters can progress disease states when active. Indeed aberrant activation of retrotransposon derived promoters in cancer can lead to transcription of oncogenic isoforms of cellular genes. Here we propose that activation of promoters of transposable elements in cancer can also drive transcription of long non-coding RNAs whose expression leads to silencing of linked tumor suppressor genes. Such transcription driven by aberrantly active transposable elements in cancer can lead to a characteristic reprogramming of epigenetic profiles, thus extending the potential molecular mechanisms whereby retrotransposons can directly contribute to cancer development and subsequent progression.
authors.affiliation: School of Medicine; University of Nottingham; Royal Derby Hospital Centre; Derby, England UK ; Centre for Genetics and Genomics; University of Nottingham; Nottingham, England UK.
authors.forename: Cristina
authors.initials: C
authors.lastname: Tufarelli
authors.forename: Hazel A
authors.initials: HA
authors.lastname: Cruickshanks
authors.forename: Richard R
authors.initials: RR
authors.lastname: Meehan
keywords: LINE-1 chimeric transcripts; antisense RNA; cancer; epigenetic silencing; transposable elements