Antisense now makes sense: dual modulation of androgen-dependent transcription by CTBP1-AS

Abstract

EMBO J 32 12: 1665–1680 doi:; DOI: 10.1038/emboj.2013.99; published online May 03 2013

Recent advances in genomic approaches for exploring the transcriptome have led to the identification of thousands of novel non-coding RNA (ncRNA) transcripts (Djebali et al, 2012). While some of these ncRNAs have been implicated in the development and progression of cancer and other human diseases, their underlying mechanisms of action remain largely unknown (Esteller, 2011). Takayama et al (2013) now report the identification of CTBP1-AS, a novel androgen-regulated long ncRNA that promotes prostate cancer growth through sense–antisense repression of the transcriptional co-regulator CTBP1, as well as through the global epigenetic regulation of tumour suppressor genes.

Figure 1

Proposed model of CTBP1-AS regulation of androgen-dependent gene expression. Ligand-bound androgen receptor (AR) induces the expression of CTBP1-AS, which binds and recruits PSF and HDAC/Sin3A complex to the promoter of CTBP1, resulting in histone deacetylation and inhibition of CTBP1 expression. The decrease in CTBP1 level brings about H3K9 demethylation at AR binding sites and the de-repression of androgen-induced genes. CTBP1-AS also cooperates with PSF and HDAC/Sin3A complex to mediate the global repression of androgen-regulated genes, such as p53 and SMAD3.