The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation
| Autor: | Laura Santangelo, Marco Tripodi, Cecilia Battistelli, Frank J. Gonzalez, Carla Cicchini, Giovanna Sabarese, Claudia Montaldo |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Carcinoma Hepatocellular Epithelial-Mesenchymal Transition Biology Article Mice 03 medical and health sciences 0302 clinical medicine Transcription (biology) snail Transcriptional regulation Animals Humans Hox gene Molecular Biology epigenetics Liver Neoplasms EMT RNA Cell Differentiation HOTAIR Oncogenes Cell Biology Chromatin LncRNA Long non-coding RNA Cell biology Gene Expression Regulation Neoplastic Hepatocyte nuclear factors 030104 developmental biology Gene Expression Regulation Hepatocyte Nuclear Factor 4 030220 oncology & carcinogenesis Hepatocytes RNA Long Noncoding Snail Family Transcription Factors |
| Zdroj: | Cell Death and Differentiation |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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