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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
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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.
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Overall design |
mRNA profiles of HCT116 wild type (WT), HCT116 ARID1A Knockout(KO), and HCT116 ARID1A KO and HERVH knockdown(KD) cells.
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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
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Submission date |
Jul 20, 2021 |
Last update date |
Jun 28, 2022 |
Contact name |
Jiale Chen |
E-mail(s) |
jl_chen1@outlook.com
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Phone |
+8619198255113
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Organization name |
Central South University
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Department |
Human Key Laboratory of Medical Genetics
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Street address |
Kaifu district, Xiangya road
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City |
Changsha |
State/province |
Hunan |
ZIP/Postal code |
410000 |
Country |
China |
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Platforms (1) |
GPL16791 |
Illumina HiSeq 2500 (Homo sapiens) |
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Samples (34)
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Relations |
BioProject |
PRJNA748378 |
SRA |
SRP329118 |