Reciprocal regulation of chromatin state and architecture by HOTAIRM1 contributes to temporal collinear HOXA gene activation

Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many of which represent important regulators of gene expression. However, the mechanisms used by lncRNAs to control transcription remain largely uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker in...

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Veröffentlicht in:	Nucleic acids research Jg. 45; H. 3; S. gkw966 - 1104
Hauptverfasser:	Wang, Xue Q. D., Dostie, Josée
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	England Oxford University Press 17.02.2017
Schlagworte:	Cell Line, Tumor Chromatin - genetics Chromatin - metabolism Gene Expression Profiling Gene Knockdown Techniques Gene regulation, Chromatin and Epigenetics Genes, Homeobox Histone Demethylases - metabolism Histone-Lysine N-Methyltransferase - metabolism Homeodomain Proteins - genetics Humans MicroRNAs - antagonists & inhibitors MicroRNAs - genetics MicroRNAs - metabolism Models, Genetic Myeloid-Lymphoid Leukemia Protein - metabolism Nuclear Proteins - metabolism Polycomb Repressive Complex 2 - metabolism RNA Interference Transcriptional Activation - drug effects Tretinoin - pharmacology
ISSN:	0305-1048, 1362-4962, 1362-4962
Online-Zugang:	Volltext
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Zusammenfassung:	Thousands of long non-coding RNAs (lncRNAs) have been identified in mammals, many of which represent important regulators of gene expression. However, the mechanisms used by lncRNAs to control transcription remain largely uncharacterized. Here, we report on HOTAIRM1, a promising lncRNA biomarker in leukemia and solid tumors. We find that HOTAIRM1 contributes to three-dimensional chromatin organization changes required for the temporal collinear activation of HOXA genes. We show that distinct HOTAIRM1 variants preferentially associate with either UTX/MLL or PRC2 complexes to modulate the levels of activating and silencing marks at the bivalent domain. HOTAIRM1 contributes to physical dissociation of chromatin loops at the cluster proximal end, which delays recruitment of the histone demethylase UTX and transcription of central HOXA genes. Interestingly, we find overall proximal HOXA gene activation without chromatin conformation changes by HOTAIRM1 in a different cell type. Our results reveal a previously unappreciated relationship between chromatin structure, architecture and lncRNA function.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0305-1048 1362-4962 1362-4962
DOI:	10.1093/nar/gkw966