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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.
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
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
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). | 150 | |
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. | Top 1% | |
influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically). | Top 10% | |
impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network. | Top 1% |