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| Status |
Public on May 20, 2022 |
| Title |
RPB1 ChIP-Seq of adrenal glands tissue from Wild Type (WT) and Armc5 knockout mice |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
RPB1-specific ubiquitin ligase (E3) controls the degradation of this largest subunit of Pol II and consequently the Pol II pool size. Although several RPB1-specific E3s have been documented, their function is only revealed in cells with massive DNA damage. We demonstrated that ARMC5 physically interacted with cullin3 (CUL3) and RPB1. ARMC5 is an armadillo domain-containing protein with unknown mechanisms of action. ARMC5 deletion caused significant RPB1 accumulation in all the major organs under a physiological condition in the absence of artificially induced DNA damage. This is accompanied by reduced RPB1 ubiquitination. In vitro ubiquitination assay proved that ARMC5, CUL3, and RBX1 formed an effective E3 for RPB1. RPB1 was confirmed as being highly accumulated in the adrenal gland nodules from PBMAH patients with mutations in the ARMC5 coding sequence. Surprisingly, the compromised RPB1 degradation did not lead to increased Pol II stalling according to ChIP-Seq, or a general decrease of gene transcription according to RNA-seq. On the contrary, among 1486 differentially expressed genes in the KO adrenal glands, 93.5% of them were upregulated, probably due to the enlarged Pol II pool size. Our results showed that the ARMC3-CUL3 E3 was the dominant E3 in normal cells and organs and controlled Pol II pool size. The abnormally large Pol II pool size due to ARMC5 mutation dysregulated a large number of genes that in turn led to many phenotypes, including PBMAH in humans.
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| Overall design |
ChIP-Seq profiles of RPB1(NTD)-specific antibody for adrenal glands tissue from WT and Armc5(-/-) mice
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| Contributor(s) |
Lao L, Wu J, Luo H |
| Citation(s) |
35687106 |
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| Submission date |
Mar 24, 2021 |
| Last update date |
Jul 07, 2022 |
| Contact name |
Jiangping Wu |
| E-mail(s) |
jianping.wu@umontreal.ca
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| Organization name |
CR.CHUM
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| Street address |
900 Rue Saint Denis
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| City |
Montreal |
| ZIP/Postal code |
H2X0A9 |
| Country |
Canada |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (6)
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| Relations |
| BioProject |
PRJNA717038 |
| SRA |
SRP312024 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE169578_AG.counts_data.tsv.gz |
500.4 Kb |
(ftp)(http) |
TSV |
| GSE169578_AG.log2cpm_data.tsv.gz |
1.5 Mb |
(ftp)(http) |
TSV |
| GSE169578_AG_GENEBODY.counts_data.csv.gz |
203.1 Kb |
(ftp)(http) |
CSV |
| GSE169578_AG_TES.counts_data.csv.gz |
153.4 Kb |
(ftp)(http) |
CSV |
| GSE169578_AG_TSS.counts_data.csv.gz |
159.3 Kb |
(ftp)(http) |
CSV |
| GSE169578_RAW.tar |
2.9 Gb |
(http)(custom) |
TAR (of BW) |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data provided as supplementary file |
| Processed data are available on Series record |
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