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Series GSE121808 Query DataSets for GSE121808
Status Public on Jan 01, 2019
Title Enhancer associated long non-coding RNA transcription and immune gene regulation in experimental models of rickettsial infection
Organism Mus musculus
Experiment type Non-coding RNA profiling by high throughput sequencing
Summary Recent discovery that much of the mammalian genome does not encode protein-coding genes (PCGs) has brought widespread attention to long noncoding RNAs (lncRNAs) as a novel layer of biological regulation. Enhancer lnc (elnc) RNAs from the enhancer regions of the genome carry the capacity to regulate PCGs in cis or in trans. Spotted fever rickettsioses represent the consequence of host infection with Gram-negative, obligate intracellular bacteria in the Genus Rickettsia. Despite being implicated in the pathways of infection and inflammation, the roles of lncRNAs in host response to Rickettsia species have remained a mystery. We have profiled the expression of host lncRNAs during infection of susceptible mice with R. conorii as a model closely mimicking the pathogenesis of human spotted fever rickettsioses. RNA sequencing on the lungs of infected hosts yielded reads mapping to 74,964 non-coding RNAs, 206 and 277 of which were determined to be significantly up- and down-regulated in comparison to uninfected controls. Following removal of short non-coding RNAs and ambiguous transcripts, remaining transcripts underwent in-depth analysis of mouse lung epigenetic signatures H3K4Me1 and H3K4Me3, active transcript markers (POLR2A, p300, CTCF), and DNaseI hypersensitivity sites to identify two potentially active and highly up-regulated elncRNAs NONMMUT013718 and NONMMUT024103. Using Hi-3C sequencing resource, we further determined that genomic loci of NONMMUT013718 and NONMMUT024103 might interact with and regulate the expression of nearby PCGs, namely Id2 (inhibitor of DNA binding 2) and Apol10b (apolipoprotein 10b), respectively. Heterologous reporter assays confirmed the activity of elncRNAs as the inducers of their predicted PCGs. In the lungs of infected mice, expression of both elncRNAs and their targets was significantly higher than mock-infected controls. Induced expression of NONMMUT013718/Id2 in murine macrophages and NONMMUT024103/Apol10b in endothelial cells was also clearly evident during R. conorii infection in vitro. Finally, shRNA mediated knock-down of NONMMUT013718 and NONMMUT024103 elncRNAs resulted in reduced expression of endogenous Id2 and Apl10b, demonstrating the regulatory roles of these elncRNAs on their target PCGs. Our results provide very first experimental evidence suggesting altered expression of pulmonary lncRNAs and elncRNA-mediated regulation of PCGs involved in immunity and during host interactions with pathogenic rickettsiae.
Overall design Examination of expression of long non coding RNA's in mice infected with R. conorii in comparison to non infected mice.
Contributor(s) Chowdhury IH, Narra HP, Sahni A, Khanipov K, Fofanov Y, Sahni SK
Citation(s) 30687302
Submission date Oct 25, 2018
Last update date Feb 06, 2019
Contact name Kamil Khanipov
Organization name University of Texas Medical Branch
Street address 301 University Blvd
State/province TX
ZIP/Postal code 77555
Country USA
Platforms (1)
GPL18480 Illumina HiSeq 1500 (Mus musculus)
Samples (6)
GSM3446996 mouse1a
GSM3446997 mouse1b
GSM3446998 mouse3
BioProject PRJNA498498
SRA SRP166884

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Supplementary file Size Download File type/resource
GSE121808_Mouse_lncRNA_Mapping.xlsx 8.7 Mb (ftp)(http) XLSX
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Raw data are available in SRA
Processed data are available on Series record

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