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Polymorphic endogenous retroviral element gives rise to differential epigenomic states and gene expression between distinct genetic backgrounds

ABSTRACT: Polymorphic integrations of endogenous retroviruses (ERVs) have been previously detected in mouse and human genomes. While most are inert, a subset is capable of influencing the activity of the host genes. However, the molecular mechanism underlying how such elements affect the epigenome and transcriptome and their roles in driving intra-specific variation remain unclear. Here, utilizing wildtype murine embryonic stem cells (mESCs) derived from distinct genetic backgrounds, we discovered a polymorphic MMERGLN element capable of regulating H3K27ac enrichment, transcription and higher-order chromatin structure of neighboring loci. We demonstrated that this polymorphic element enhanced the neighboring Klhdc4 gene’s expression in cis, which in turn altered activity of downstream stress response genes. The results suggest that the polymorphic ERV-derived cis-regulatory element contribute to strain-specific phenotypes from particular stimuli. Moreover, we identified thousands of potential polymorphic ERVs in mESCs from both strains and illustrated their potential to regulate nearby histone modifications and transcription. Overall, our findings show the mechanism of how polymorphic ERVs can shape the epigenome and transcriptional networks that give rise to phenotypic divergence between individuals.

ORGANISM(S): Mus musculus

PROVIDER: GSE165214 | GEO | 2021/09/22

REPOSITORIES: GEO

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