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Series GSE169582 Query DataSets for GSE169582
Status Public on Dec 01, 2023
Title RPB1 ChIP-Seq of NSC from Wild Type (WT) and Armc5 knockout mice
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary ARMC5 is a protein containing an armadillo domain (ARM) and a BTB domain. Its gene knockout caused many phenotypes, including dwarfism, compromise T-cell immunity, and adrenal gland hypertrophy. ARMC5 mutation in humans is associated with bilateral macronodular adrenal gland hypertrophy. We found that AMC5 KO mice suffered from an increased incidence of neural tube defects (NTDs). We revealed that ARMC5 complexed with CUL3 and POLR2A and was part of a novel POLR2A-specific ubiquitin ligase (E3). This E3 was the dominant DNA damage-independent POLR2A-specific E3 in developing neural tubes and neural precursor cells under a physiological condition. ARMC5 gene knockout (KO) caused diminished POLR2A ubiquitination and compromised POLR2A degradation via proteasomes. Surprisingly, the absence of this E3 did not lead to generalized Pol II stalling and the subsequent generalized decrease of mRNA transcription but caused an enlarged Pol II pool size, which dysregulated 108 genes in NPCs, including some known to neural development. ARMC5 KO in the intestine downregulated FOHL1 expression, which was essential in folate absorption. Whole-exome sequencing of 511 myelomeningocele (MM) patients revealed nine highly deleterious mutations in the ARMC5 coding sequence. A significant deleterious mutation Arg429Cys found in MM patients drastically weakened the interaction between ARMC5 and POLR2A, supporting our hypothesis that such mutations in ARMC5 increased the NTD risks by compromising the POLR2A-specific E3 activity. Our results indicated that this novel ARMC5-CUL3-RBX1 E3 played a critical role in Pol II pool homeostasis, and ARMC5 mutation was a modifier of NTD risks in mice and humans.
Overall design RPB1 ChIP-Seq profiles of Neural stem cell from WT and Armc5(-/-) mice
Contributor(s) Lao L, Wu J, Luo H
Citation(s) 38225631
Submission date Mar 24, 2021
Last update date Jan 29, 2024
Contact name Jiangping Wu
Organization name CR.CHUM
Street address 900 Rue Saint Denis
City Montreal
ZIP/Postal code H2X0A9
Country Canada
Platforms (1)
GPL24247 Illumina NovaSeq 6000 (Mus musculus)
Samples (6)
GSM5210276 ARMC5_WT_NSC 1
GSM5210277 ARMC5_WT_NSC 2
GSM5210278 ARMC5_WT_NSC 3
BioProject PRJNA717040
SRA SRP312023

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE169582_NSC.counts_data.tsv.gz 469.2 Kb (ftp)(http) TSV
GSE169582_NSC.log2cpm_data.tsv.gz 1.4 Mb (ftp)(http) TSV
GSE169582_NSC_GENEBODY.counts_data.csv.gz 191.6 Kb (ftp)(http) CSV
GSE169582_NSC_TES.counts_data.csv.gz 140.6 Kb (ftp)(http) CSV
GSE169582_NSC_TSS.counts_data.csv.gz 149.6 Kb (ftp)(http) CSV
GSE169582_RAW.tar 3.4 Gb (http)(custom) TAR (of BW)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file
Processed data are available on Series record

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