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The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis

A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA–TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic R...

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Autores principales: Herriges, Michael J., Tischfield, David J., Cui, Zheng, Morley, Michael P., Han, Yumiao, Babu, Apoorva, Li, Su, Lu, MinMin, Cendan, Isis, Garcia, Benjamin A., Anderson, Stewart A., Morrisey, Edward E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cold Spring Harbor Laboratory Press 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458756/
https://www.ncbi.nlm.nih.gov/pubmed/28546511
http://dx.doi.org/10.1101/gad.298018.117
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author Herriges, Michael J.
Tischfield, David J.
Cui, Zheng
Morley, Michael P.
Han, Yumiao
Babu, Apoorva
Li, Su
Lu, MinMin
Cendan, Isis
Garcia, Benjamin A.
Anderson, Stewart A.
Morrisey, Edward E.
author_facet Herriges, Michael J.
Tischfield, David J.
Cui, Zheng
Morley, Michael P.
Han, Yumiao
Babu, Apoorva
Li, Su
Lu, MinMin
Cendan, Isis
Garcia, Benjamin A.
Anderson, Stewart A.
Morrisey, Edward E.
author_sort Herriges, Michael J.
collection PubMed
description A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA–TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)–Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in cis to promote Nkx2.1 transcription. Although loss of NANCI alone does not adversely affect lung development, concurrent heterozygous mutations in both NANCI and Nkx2.1 leads to persistent Nkx2.1 deficiency and reprogramming of lung epithelial cells to a posterior endoderm fate. This disruption in the NANCI–Nkx2.1 gene duplex results in a defective perinatal innate immune response, tissue damage, and progressive degeneration of the adult lung. These data point to a mechanism in which lncRNAs act as rheostats within lncRNA–TF gene duplex loci that buffer TF expression, thereby maintaining tissue-specific cellular identity during development and postnatal homeostasis.
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spelling pubmed-54587562017-11-01 The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis Herriges, Michael J. Tischfield, David J. Cui, Zheng Morley, Michael P. Han, Yumiao Babu, Apoorva Li, Su Lu, MinMin Cendan, Isis Garcia, Benjamin A. Anderson, Stewart A. Morrisey, Edward E. Genes Dev Research Paper A subset of long noncoding RNAs (lncRNAs) is spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA–TF gene duplexes regulate tissue development and homeostasis is unclear. We identified a feedback loop within the NANCI (Nkx2.1-associated noncoding intergenic RNA)–Nkx2.1 gene duplex that is essential for buffering Nkx2.1 expression, lung epithelial cell identity, and tissue homeostasis. Within this locus, Nkx2.1 directly inhibits NANCI, while NANCI acts in cis to promote Nkx2.1 transcription. Although loss of NANCI alone does not adversely affect lung development, concurrent heterozygous mutations in both NANCI and Nkx2.1 leads to persistent Nkx2.1 deficiency and reprogramming of lung epithelial cells to a posterior endoderm fate. This disruption in the NANCI–Nkx2.1 gene duplex results in a defective perinatal innate immune response, tissue damage, and progressive degeneration of the adult lung. These data point to a mechanism in which lncRNAs act as rheostats within lncRNA–TF gene duplex loci that buffer TF expression, thereby maintaining tissue-specific cellular identity during development and postnatal homeostasis. Cold Spring Harbor Laboratory Press 2017-05-01 /pmc/articles/PMC5458756/ /pubmed/28546511 http://dx.doi.org/10.1101/gad.298018.117 Text en © 2017 Herriges et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by-nc/4.0/ This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Research Paper
Herriges, Michael J.
Tischfield, David J.
Cui, Zheng
Morley, Michael P.
Han, Yumiao
Babu, Apoorva
Li, Su
Lu, MinMin
Cendan, Isis
Garcia, Benjamin A.
Anderson, Stewart A.
Morrisey, Edward E.
The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title_full The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title_fullStr The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title_full_unstemmed The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title_short The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
title_sort nanci–nkx2.1 gene duplex buffers nkx2.1 expression to maintain lung development and homeostasis
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5458756/
https://www.ncbi.nlm.nih.gov/pubmed/28546511
http://dx.doi.org/10.1101/gad.298018.117
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