ARID1A loss derepresses a group of human endogenous retrovirus-H loci to modulate BRD4-dependent transcription.

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 pa

SUBMITTER: Yu C 

PROVIDER: S-EPMC9205910 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature