A unique active role for HOTAIR to promote transcription in prostate cancer progression

ABSTRACT: Previous research has predominantly focused on the regulatory role of lncRNA HOTAIR in gene silencing through its interaction with the Polycomb repressive complex 2 (PRC2). Here, our study uncovers a novel regulatory mechanism of HOTAIR, which facilitates prostate cancer (PCa) progression by sustaining transcription elongation. Using ChIRP-seq, RNA-seq, and ChIP-seq, we successfully mapped the binding sites of HOTAIR across the genome and determined their interplay with the epigenetic landscape. We discovered that the co-localization of HOTAIR with the androgen receptor (AR) can activate gene transcription. In the context of AR binding, we discovered that HOTAIR maintains transcription elongation by facilitating the formation of the CDK9/Pol2S2 complex. We revealed a unique capacity of HOTAIR to promote transcriptional activation on gene promoters/bodies with low H3K27me3 enrichment, a function contrasting to its established PRC2-related transcriptional inhibitory roles in regions with high H3K27me3 signal. Finally, we identified two direct target genes of HOTAIR (MMP14 and TNFAIP2), which contribute to the progression of PCa. Collectively, our research sheds new light on HOTAIR's role in transcriptional regulation, offering potential therapeutic strategies and expand our understanding of HOTAIR's roles in PCa progression. In this study, we used ChIRP-seq to identify HOTAIR binding sites on genome-wide of PCa cells. Then, for purpose of associating chromatin location of HOTAIR to epigenetic landscape, we profiled repressed histone mark (H3K27me3) and active histone mark (H3K27ac). Finally, we integrated data of ChIRP-seq, RNA-seq and ChIP-seq for a complete analysis. We identified that HOTAIR can co-locate with AR to enhance transcription elongation on low H3K27m3 enrichment gene body/promoter, which differs from the function of HOTAIR on high H3K27me3 enrichment region.

ORGANISM(S): Homo sapiens

PROVIDER: GSE221263 | GEO | 2024/03/26

REPOSITORIES: GEO