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Genes & Development
Article
License: CC BY NC
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PubMed Central
Other literature type . 2014
License: CC BY NC
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Genes & Development
Article . 2014 . Peer-reviewed
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Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development

Authors: Herriges, Michael J; Swarr, Daniel T; Morley, Michael P; Rathi, Komal S; Peng, Tien; Stewart, Kathleen M; Morrisey, Edward E;

Long noncoding RNAs are spatially correlated with transcription factors and regulate lung development

Abstract

Long noncoding RNAs (lncRNAs) are thought to play important roles in regulating gene transcription, but few have well-defined expression patterns or known biological functions during mammalian development. Using a conservative pipeline to identify lncRNAs that have important biological functions, we identified 363 lncRNAs in the lung and foregut endoderm. Importantly, we show that these lncRNAs are spatially correlated with transcription factors across the genome. In-depth expression analyses of lncRNAs with genomic loci adjacent to the critical transcription factors Nkx2.1, Gata6, Foxa2 (forkhead box a2), and Foxf1 mimic the expression patterns of their protein-coding neighbor. Loss-of-function analysis demonstrates that two lncRNAs, LL18/NANCI (Nkx2.1-associated noncoding intergenic RNA) and LL34, play distinct roles in endoderm development by controlling expression of critical developmental transcription factors and pathways, including retinoic acid signaling. In particular, we show that LL18/NANCI acts upstream of Nkx2.1 and downstream from Wnt signaling to regulate lung endoderm gene expression. These studies reveal that lncRNAs play an important role in foregut and lung endoderm development by regulating multiple aspects of gene transcription, often through regulation of transcription factor expression.

Country
United States
Keywords

570, 1.1 Normal biological development and functioning, Thyroid Nuclear Factor 1, 610, Medical and Health Sciences, lung, Cell Line, Mice, lncRNA, Underpinning research, Genetics, retinoic acid, Animals, Humans, Developmental, development, Lung, Wnt Signaling Pathway, Genome, Gene Expression Profiling, Human Genome, Psychology and Cognitive Sciences, Endoderm, Gene Expression Regulation, Developmental, Nuclear Proteins, Cell Differentiation, Biological Sciences, Wnt signaling, Nkx2.1, HEK293 Cells, Gene Expression Regulation, Gene Knockdown Techniques, RNA, Long Noncoding, RNA, Long Noncoding, Resource/Methodology, Biotechnology, Developmental Biology, Transcription Factors

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    This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
    Top 1%
    influence
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    impulse
    This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
    Top 1%
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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
150
Top 1%
Top 10%
Top 1%
Green
Published in a Diamond OA journal