The LncRNA HOTAIR Transcription is Controlled by HNF4α-induced Chromatin Topology Modulation

Overview

Journal Cell Death Differ

Specialty Cell Biology

Date 2018 Aug 30

PMID 30154449

Citations 35

Authors

Cecilia Battistelli

Giovanna Sabarese

Laura Santangelo

Claudia Montaldo

Frank J Gonzalez

Marco Tripodi

Carla Cicchini

Affiliations

Soon will be listed here.

Abstract

The expression of the long noncoding RNA HOTAIR (HOX Transcript Antisense Intergenic RNA) is largely deregulated in epithelial cancers and positively correlates with poor prognosis and progression of hepatocellular carcinoma and gastrointestinal cancers. Furthermore, functional studies revealed a pivotal role for HOTAIR in the epithelial-to-mesenchymal transition, as this RNA is causal for the repressive activity of the master factor SNAIL on epithelial genes. Despite the proven oncogenic role of HOTAIR, its transcriptional regulation is still poorly understood. Here hepatocyte nuclear factor 4-α (HNF4α), as inducer of epithelial differentiation, was demonstrated to directly repress HOTAIR transcription in the mesenchymal-to epithelial transition. Mechanistically, HNF4α was found to cause the release of a chromatin loop on HOTAIR regulatory elements thus exerting an enhancer-blocking activity.

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