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Series GSE180475 Query DataSets for GSE180475
Status Public on Jul 21, 2021
Title ARID1A loss derepresses human endogenous retrovirus-H to modulate BRD4-dependent transcription
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
Summary Purpose: The transposable elements (TEs) through evolutionary exaptation have become an integral part of human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis are recognized, their role in malignancy has only started to emerge.
Results: Here we show that many TEs, especially the pluripotency-related endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. The transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors including ARID1A. Knockout of ARID1A in CRC cells leads to increased accessibility at HERVH loci and enhanced transcription, which is dependent on ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulate their dynamics, and co-regulate many target genes.
Conclusions: Altogether, we uncover a critical role for ARID1A in restraining HERVH, which can promote tumorigenesis by stimulating BRD4-dependent transcription when ARID1A is mutated.
 
Overall design mRNA profiles of HCT116 wild type (WT), HCT116 ARID1A Knockout(KO), and HCT116 ARID1A KO and HERVH knockdown(KD) cells.
 
Contributor(s) Lei X, Yu C, Chen J, Yuan K
Citation(s)
  • Yu C, Lei X, Chen F, Mao S et al. ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription. Nat Commun 2022 Jun 17;13(1):3501. PMID: 35715442
Submission date Jul 20, 2021
Last update date Jun 28, 2022
Contact name Jiale Chen
E-mail(s) jl_chen1@outlook.com
Phone +8619198255113
Organization name Central South University
Department Human Key Laboratory of Medical Genetics
Street address Kaifu district, Xiangya road
City Changsha
State/province Hunan
ZIP/Postal code 410000
Country China
 
Platforms (1)
GPL16791 Illumina HiSeq 2500 (Homo sapiens)
Samples (34)
GSM5463588 1.HCT116.WT.shGFP.rep1
GSM5463589 2.HCT116.WT.shGFP.rep2
GSM5463590 3.HCT116.WT.shHERVH#1.rep1
Relations
BioProject PRJNA748378
SRA SRP329118

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
GSE180475_table_1.sample_1-8_genes_CPM.xlsx 2.6 Mb (ftp)(http) XLSX
GSE180475_table_2.sample_9-26_genes_raw_counts.txt.gz 669.8 Kb (ftp)(http) TXT
GSE180475_table_3._sample_27-34_genes_raw_counts.txt.gz 374.1 Kb (ftp)(http) TXT
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Raw data are available in SRA
Processed data are available on Series record

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