The lncRNA HOTAIR transcription is controlled by HNF4α-induced chromatin topology modulation.
Animals
Carcinoma, Hepatocellular
/ genetics
Cell Differentiation
/ genetics
Chromatin
/ genetics
Epithelial-Mesenchymal Transition
/ genetics
Gene Expression Regulation
/ genetics
Gene Expression Regulation, Neoplastic
/ genetics
Hepatocyte Nuclear Factor 4
/ genetics
Hepatocytes
/ metabolism
Humans
Liver Neoplasms
/ genetics
Mice
RNA, Long Noncoding
/ genetics
Snail Family Transcription Factors
/ genetics
Journal
Cell death and differentiation
ISSN: 1476-5403
Titre abrégé: Cell Death Differ
Pays: England
ID NLM: 9437445
Informations de publication
Date de publication:
05 2019
05 2019
Historique:
received:
18
05
2018
accepted:
03
07
2018
revised:
02
07
2018
pubmed:
30
8
2018
medline:
7
7
2020
entrez:
30
8
2018
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 30154449
doi: 10.1038/s41418-018-0170-z
pii: 10.1038/s41418-018-0170-z
pmc: PMC6461983
doi:
Substances chimiques
Chromatin
0
HOTAIR long non-coding RNA, mouse
0
Hepatocyte Nuclear Factor 4
0
Hnf4a protein, mouse
0
RNA, Long Noncoding
0
Snai1 protein, mouse
0
Snail Family Transcription Factors
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
890-901Références
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