Gv1, a Zinc Finger Gene Controlling Endogenous MLV Expression

Area of Science:

• Genetics
• Virology
• Epigenetics

Background:

• Inbred mice possess approximately 50 endogenous murine leukemia virus (MLV) loci, with strain-specific variations.
• The Gv1 locus regulates endogenous MLV transcription and MLV envelope (GIX antigen) cell-surface expression.

Purpose of the Study:

• To identify the gene responsible for the Gv1 locus function.
• To elucidate the mechanism by which Zfp998 determines the GIX+ phenotype and regulates endogenous MLVs.

Main Methods:

• Long-read sequencing of bacterial artificial chromosome clones from 129 mice.
• Functional analysis of Zfp998 to assess its necessity and sufficiency for the GIX+ phenotype.

Main Results:

• A single Krüppel-associated box zinc finger protein (ZFP) gene, Zfp998, was identified as the Gv1 locus.
• Splice-acceptor variations in Zfp998 were found to be responsible for both the sufficiency and deficiency of GIX+ phenotype determination.
• The study highlighted diverse origins of the chromosomal region containing Gv1.

Conclusions:

• Zfp998 is the Gv1 locus, essential for GIX antigen presentation and endogenous MLV regulation.
• Zfp998 is the second ZFP gene identified to epigenetically suppress endogenous MLVs in mice.
• Zinc finger protein genes play a significant role in controlling endogenous retroviruses in mice.