» Articles » PMID: 35715442

ARID1A Loss Derepresses a Group of Human Endogenous Retrovirus-H Loci to Modulate BRD4-dependent Transcription

Overview
Journal Nat Commun
Specialty Biology
Date 2022 Jun 17
PMID 35715442
Authors
Affiliations
Soon will be listed here.
Abstract

Transposable elements (TEs) through evolutionary exaptation have become an integral part of the human genome, offering ample regulatory sequences and shaping chromatin 3D architecture. While the functional impacts of TE-derived sequences on early embryogenesis have been recognized, their roles in malignancy are only starting to emerge. Here we show that many TEs, especially the pluripotency-related human endogenous retrovirus H (HERVH), are abnormally activated in colorectal cancer (CRC) samples. Transcriptional upregulation of HERVH is associated with mutations of several tumor suppressors, particularly ARID1A. Knockout of ARID1A in CRC cells leads to increased transcription at several HERVH loci, which involves compensatory contribution by ARID1B. Suppression of HERVH in CRC cells and patient-derived organoids impairs tumor growth. Mechanistically, HERVH transcripts colocalize with nuclear BRD4 foci, modulating their dynamics and co-regulating many target genes. Altogether, we uncover a critical role for ARID1A in restraining HERVH, whose abnormal activation can promote tumorigenesis by stimulating BRD4-dependent transcription.

Citing Articles

Reducing batch effects in single cell chromatin accessibility measurements by pooled transposition with MULTI-ATAC.

Conrad D, Phong K, Korotkevich E, McGinnis C, Zhu Q, Chow E bioRxiv. 2025; .

PMID: 40027737 PMC: 11870453. DOI: 10.1101/2025.02.14.638353.


HERV Modulation in Colorectal Carcinoma Patients: A Snapshot of Endogenous Retroviral Transcriptome.

Grandi N, Liu C, Chabukswar S, Carta D, Yen Y, Lin L J Med Virol. 2025; 97(3):e70249.

PMID: 39992019 PMC: 11849272. DOI: 10.1002/jmv.70249.


FBXO31-mediated ubiquitination of OGT maintains O-GlcNAcylation homeostasis to restrain endometrial malignancy.

Zhang N, Meng Y, Mao S, Ni H, Huang C, Shen L Nat Commun. 2025; 16(1):1274.

PMID: 39894887 PMC: 11788441. DOI: 10.1038/s41467-025-56633-z.


The virome composition of respiratory tract changes in school-aged children with Mycoplasma pneumoniae infection.

Zhang D, Cao Y, Dai B, Zhang T, Jin X, Lan Q Virol J. 2025; 22(1):10.

PMID: 39806507 PMC: 11731546. DOI: 10.1186/s12985-025-02626-9.


Advances in the study of the role of high-frequency mutant subunits of the SWI/SNF complex in tumors.

Zhao J, Zhu J, Tang Y, Zheng K, Li Z Front Oncol. 2024; 14:1463892.

PMID: 39697230 PMC: 11652375. DOI: 10.3389/fonc.2024.1463892.


References
1.
Feschotte C, Gilbert C . Endogenous viruses: insights into viral evolution and impact on host biology. Nat Rev Genet. 2012; 13(4):283-96. DOI: 10.1038/nrg3199. View

2.
Thompson P, Macfarlan T, Lorincz M . Long Terminal Repeats: From Parasitic Elements to Building Blocks of the Transcriptional Regulatory Repertoire. Mol Cell. 2016; 62(5):766-76. PMC: 4910160. DOI: 10.1016/j.molcel.2016.03.029. View

3.
Chuong E, Elde N, Feschotte C . Regulatory activities of transposable elements: from conflicts to benefits. Nat Rev Genet. 2016; 18(2):71-86. PMC: 5498291. DOI: 10.1038/nrg.2016.139. View

4.
Cosby R, Chang N, Feschotte C . Host-transposon interactions: conflict, cooperation, and cooption. Genes Dev. 2019; 33(17-18):1098-1116. PMC: 6719617. DOI: 10.1101/gad.327312.119. View

5.
Rebollo R, Romanish M, Mager D . Transposable elements: an abundant and natural source of regulatory sequences for host genes. Annu Rev Genet. 2012; 46:21-42. DOI: 10.1146/annurev-genet-110711-155621. View