Expression and regulation of human endogenous retrovirus W elements

Area of Science:

• Genomics
• Molecular Biology
• Immunology

Background:

• Human endogenous retroviruses (HERV) constitute 8% of the human genome, with distinct families and proviral structures.
• HERVs, largely repetitive and lacking protein-coding capacity, have been overlooked in expression studies.
• The HERV-W family is increasingly recognized for its expression in various human tissues, particularly the placenta.

Purpose of the Study:

• To investigate the expression, regulation, and functional significance of the HERV-W family.
• To explore the role of HERV-W long terminal repeats (LTRs) in transcriptional regulation.
• To understand the association of HERV-W aberrant expression with human diseases and environmental exposures.

Main Methods:

• Analysis of HERV-W expression patterns in different human tissues and cell lines.
• Investigation of HERV-W LTRs as promoters and enhancers.
• Examination of factors influencing HERV-W transcription, including transcription factors, genetic variation, and epigenetic modifications (DNA methylation, histone modification).

Main Results:

• HERV-W LTRs drive tissue-specific and diverse expression of HERV-W members.
• Leaky transcription from adjacent genes contributes to HERV-W transcription initiation.
• HERV-W elements, including ERVWE1, can be transactivated during viral infections and are associated with diseases like cancer, multiple sclerosis, and schizophrenia.

Conclusions:

• HERV-W transcriptional activity is regulated by LTRs, external enhancers, genetic variation, and epigenetic changes.
• HERV-W may serve as a marker or mediator of environmental exposures, such as viral infections, in the pathogenesis of chronic complex diseases.