The Landscape of HervRNAs Transcribed from Human Endogenous Retroviruses Across Human Body Sites

Overview

Journal Genome Biol

Specialties Biology
Genetics

Date 2022 Nov 4

PMID 36329469

Authors

Jianqi She

Minghao Du

Zhanzhan Xu

Yueqi Jin

Yu Li

Daoning Zhang

Changyu Tao

Jian Chen

Jiadong Wang

Ence Yang

Affiliations

Soon will be listed here.

Abstract

Background: Human endogenous retroviruses (HERVs), the remnants of ancient retroviruses, account for 8% of the human genome, but most have lost their transcriptional abilities under physiological conditions. However, mounting evidence shows that several expressed HERVs do exert biological functions. Here, we systematically characterize physiologically expressed HERVs and examine whether they may give insight into the molecular fundamentals of human development and disease.

Results: We systematically identify 13,889 expressed HERVs across normal body sites and demonstrate that they are expressed in body site-specific patterns and also by sex, ethnicity, and age. Analyzing cis-ERV-related quantitative trait loci, we find that 5435 hervRNAs are regulated by genetic variants. Combining this with a genome-wide association study, we elucidate that the dysregulation of expressed HERVs might be associated with various complex diseases, particularly neurodegenerative and psychiatric diseases. We further find that physiologically activated hervRNAs are associated with histone modifications rather than DNA demethylation.

Conclusions: Our results present a locus-specific landscape of physiologically expressed hervRNAs, which represent a hidden layer of genetic architecture in development and disease.

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