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Series GSE80386 Query DataSets for GSE80386
Status Public on Jun 12, 2017
Title Integrator complex subunit 12 is a key regulator of human protein synthesis pathways
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Genome wide association studies of human lung function have identified a signal on 4q24 but the mechanistic basis for this signal is unclear. This region contains the Integrator Complex subunit 12 gene (INTS12) and nearby polymorphisms associated with lung function correlate with INTS12 expression. We aimed to define INTS12 function in human bronchial epithelial cells. RNAseq pathway analyses of INTS12 depleted cells revealed robust downregulation of several protein synthesis related pathways, including the aminoacyl tRNA synthetases and PERK regulated gene expression. Indeed, INTS12 knockdown using mRNA silencing repressed cellular translation and proliferation. ChIPseq gene-centric analyses revealed INTS12 binding to be near transcriptional start sites. The binding was found to be enriched for differentially expressed loci identifying the genes it regulates, a finding previously unknown for this particular member of Integrator complex. These findings contribute to the biology behind genetic association
Overall design INTS12 depletion was induced in human bronchial epithelial cells from both donors. RNAseq gene expression profiling was performed 48h and 120h since the initiation of knockdown in the first and second donor respectively. Silencing was achieved with two independent D-siRNAs and experiments included scambled D-siRNA transfected and un-transfected cells. Experiments were performed in three biological replicates. Genome-wide INTS12 binding sites were inferred by INTS12 ChIPseq in two donor cells. ChIPseq experiment included input control pooled from both sequenced donors.
Contributor(s) Kheirallah AK
Citation(s) 28335732
Submission date Apr 18, 2016
Last update date May 15, 2019
Contact name Alexander Kheirallah
Organization name University of Cambridge
Department Stem Cell Institute
Street address Hills Road
City Cambridge
State/province Cambridgeshire
ZIP/Postal code CB2 0AH
Country United Kingdom
Platforms (2)
GPL11154 Illumina HiSeq 2000 (Homo sapiens)
GPL18573 Illumina NextSeq 500 (Homo sapiens)
Samples (27)
GSM2125479 120h_untransfected_1
GSM2125480 120h_untransfected_2
GSM2125481 120h_untransfected_3
BioProject PRJNA318778
SRA SRP073445

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Supplementary file Size Download File type/resource
GSE80386_120h_metaMatrix.txt.gz 1.4 Mb (ftp)(http) TXT
GSE80386_48h_metaMatrix.txt.gz 1.4 Mb (ftp)(http) TXT
GSE80386_RAW.tar 201.2 Mb (http)(custom) TAR (of NARROWPEAK, WIG)
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Raw data are available in SRA
Processed data are available on Series record

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