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| 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
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| 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
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| 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.
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| Contributor(s) |
Kheirallah AK |
| Citation(s) |
28335732 |
| Submission date |
Apr 18, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Alexander Kheirallah |
| E-mail(s) |
akk43@cam.ac.uk
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| Organization name |
University of Cambridge
|
| Department |
Stem Cell Institute
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| Street address |
Hills Road
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| City |
Cambridge |
| State/province |
Cambridgeshire |
| ZIP/Postal code |
CB2 0AH |
| Country |
United Kingdom |
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| Platforms (2) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
| GPL18573 |
Illumina NextSeq 500 (Homo sapiens) |
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| Samples (27)
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| Relations |
| BioProject |
PRJNA318778 |
| SRA |
SRP073445 |
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