Project description:A subset of long-noncoding RNAs (lncRNAs) are spatially correlated with transcription factors (TFs) across the genome, but how these lncRNA-TF gene duplexes regulate tissue development and homeostasis is unclear. We have identified a feedback loop within the NANCI-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 where 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.

2017-09-08 | GSE92304 | GEO

Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation [ADAR1KO HEK293T and WT MDA5]

Project description:Aberrant activation of innate immune receptors can cause a spectrum of immune disorders, such as Aicardi-Goutières syndrome (AGS). One such receptor is MDA5, a viral double-stranded RNA (dsRNA) sensor that induces antiviral immune response. We here demonstrate that constitutive activation of MDA5 in AGS results from the loss of tolerance to cellular dsRNAs formed by Alu retroelements. While wild-type MDA5 cannot efficiently recognize Alu-dsRNA because its filament formation on dsRNA is impaired by the imperfect duplex structure, AGS-variants of MDA5 display reduced sensitivity to duplex structural irregularities, assembling signaling-competent filaments on Alu-dsRNA. Moreover, we identified an unexpected role of RNA-rich cellular environment in suppressing aberrant MDA5 oligomerization, highlighting context-dependence of self vs. non-self discrimination. Overall, our work demonstrates that the increased efficiency of MDA5 to recognize dsRNA comes at a cost of self-recognition, and implicates a unique role of Alu RNAs as virus-like elements that shape the primate immune system.

2018-01-29 | GSE104864 | GEO

Breaching self-tolerance to Alu duplex RNA underlies MDA5-mediated inflammation [WT HEK293T and mutant MDA5]

2018-01-29 | GSE103539 | GEO

Association of inflammatory mediators with mitochondrial DNA mutations in geriatric COVID-19 patients

Project description:This study aimed to evaluate single nucleotide substitutions in mtDNA and analyze their correlation with inflammatory biomarkers in elderly COVID-19 patients. A total of 30 COVID-19 patients and 33 older adult controls (aged over 65 years) were enrolled. mtDNA was extracted from buffy coat samples and sequenced using a chip-based resequencing system (Affymetrix MitoChip v2.0) which detects both homoplasmic and heteroplasmic mtDNA mutations, and allows the assessment of low-level heteroplasmy. Serum concentration of IL-6, IFN-α, TNF-α and IL-10 were determined in patients by a high-sensitivity immunoassay. We found a higher burden of total heteroplasmic mutation in COVID-19 patients compared to controls with a selective increment in ND1 and COIII genes. Low-level heteroplasmy was significantly elevated in COVID-19 patients, especially in genes of the respiratory complex I. Both heteroplasmic mutation burden and low-level heteroplasmy were associated with increased levels of IL-6, TNF-α, and IFN-α.

2024-01-23 | GSE235626 | GEO

Hi-C detects novel rearrangements in HL60 and HL60/S4 cell lines

Project description:Hi-C detects novel rearrangements in HL60 and HL60/S4 cell lines

2018-12-02 | GSE120815 | GEO

PPM1D Mutations Silence NAPRT Gene Expression and Confer NAMPT Inhibitor Sensitivity in Glioma

Project description:PPM1D Mutations Silence NAPRT Gene Expression and Confer NAMPT Inhibitor Sensitivity in Glioma

| PRJNA554122 | ENA

DNA Methylation-Based High-Resolution Mapping of Long-Distance Chromosomal Interactions in Nucleosome-Depleted Regions (RNA)

Project description:Here, we present Methyltransferase Targeting-based chromosome Architecture Capture (MTAC), a method that maps the contacts between a target site (viewpoint) and the rest of the genome with high resolution and sensitivity. By targeting M.CviPI DNA methyltransferase to the viewpoint and by detecting differentially methylated regions, MTAC detects hundreds of intra- and inter-chromosomal interactions in the budding yeast genome that cannot be captured by 4C, Hi-C, or Micro-C.

2023-09-05 | GSE242399 | GEO

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