The NANCI–Nkx2.1 gene duplex buffers Nkx2.1 expression to maintain lung development and homeostasis
作者： Michael J. Herriges , David J. Tischfield , Zheng Cui , Michael P. Morley , Yumiao Han
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摘要: 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 unclear. We identified a feedback loop within NANCI (Nkx2.1-associated intergenic RNA)-Nkx2.1 duplex that essential for buffering Nkx2.1 expression, lung epithelial cell identity, homeostasis. Within this locus, directly inhibits NANCI, while acts in cis to promote transcription. Although loss alone does not adversely affect development, concurrent heterozygous mutations both leads persistent deficiency reprogramming cells posterior endoderm fate. This disruption NANCI-Nkx2.1 results defective perinatal innate immune response, damage, progressive degeneration adult lung. These data point mechanism which lncRNAs act as rheostats loci buffer TF thereby maintaining tissue-specific cellular identity during postnatal
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