Genome Biol: Expression regulation of human endogenous retroviruses

Human endogenous retrovirus (HERV) is a class of transposon elements formed by the integration of ancient retroviruses into the genome of germ cells, accounting for about 8%
of the human genome.
Most HERVs lose their normal ability to express due to sequence mutations produced during evolution and epigenetic inhibition by the host.

At this stage, more and more studies have found that the expression of some HERV has important physiological functions
in human growth and development.
Therefore, the systematic elucidating of the expression distribution law and regulatory mechanism of HERV will lay a foundation
for understanding the role of HERV in human growth and development and disease occurrence and development.

On November 3, 2022, the Yang Ence research group of Peking University School of Basic Medicine published a title in Genome Biology Paper on the landscape of hervRNAs transcribed from human endogenous retroviruses across human body sites
.
In this paper, a specific identification and quantification process for HERV sites based on the de novo assembly strategy was developed, and 13,889 physiologically expressed ones were identified in 42 human tissue sites HERV, and its expression distribution pattern, genetic regulation law and epigenetic regulation law were systematically analyzed
.

In this work, the researchers first developed a HERV site-specific identification and quantification process using the strategy of de novo assembly, and demonstrated the reliability
of the method through database comparison and experimental verification.
The method was then applied to 9466 RNA-seq samples in the GTEx database, systematically identifying a total of 13,889 tissue sites in 42 tissues site-specific expression of HERV (hervRNA), with the testes and cerebellum expressing the largest
amount of hervRNA.
Through the analysis of the expression profile of hervRNA (Figure 1), it was found that the expression of hervRNA was lower than that of mRNA and lncRNA, but its expression profile can clearly distinguish each human tissue site, which reflects the tissue site-specific expression law
of hervRNA.
The researchers then further explored the correlation between hervRNA and gender, ethnicity and age, and found that hervRNA may be associated with
brain development.

Figure 1: Physiologically expressed hervRNA
.

Subsequently, on the one hand, the researchers analyzed the genetic factors affecting HERV expression through ERV-associated quantitative trait loci (ervQTLs), and combined ervQTL with ervQTL GWAS risk locus, which found that dysregulation of expressed HERV may be associated with various complex diseases, especially psychiatric diseases and neurodegenerative diseases; On the other hand, by combining ENCODE and GTEx databases to analyze the potential epigenetic regulation of HERV expression under physiological conditions, the activated hervRNAs under physiological conditions were discovered May be associated with
histone modifications.

In conclusion, this study systematically analyzes the expression distribution law and potential regulatory mechanism of HERV under physiological conditions in a site-specific manner, which will promote our understanding of the diversity and complexity of gene expression regulatory networks, and lay a foundation
for further research on the role of HERV in human growth and development and disease occurrence and development.
Professor Yang Ence of Peking University School of Basic Medicine is the corresponding author of the paper, and Dr.
She Jianqi (Level 15 Undergraduate Study) and Dr.
Du Minghao (Grade 12 Undergraduate Doctoral Continuous Study) of Peking University School of Basic Medical Sciences are the co-first authors
of the paper.
Professor Jian Chen of Beijing Brain Science and Brain-like Research Center and Professor Wang Jiadong of Peking University School of Basic Medical Sciences gave important help
to the experimental verification work related to this paper.

Original link: https://genomebiology.
biomedcentral.
com/articles/10.
1186/s13059-022-02804-w

(School of Basic Medicine, Peking University)