# REGULATION OF ENDOGENOUS RETROVIRAL GENE EXPRESSION

> **NIH NIH R01** · SCRIPPS CLINIC AND RESEARCH FOUNDATION · 1988 · $199,897

## Abstract

The goal of this project is to elucidate in molecular terms the mechanisms
governing the expression of retroviral transcription units endogenous to
the murine genome.  Although these retroviral sequences do not result in
infectious virus they do encode viral antigens, including a distinct class
of the glycoprotein, gp70.  Recombination between these sequences and that
of infectious ecotropic virus results in the de novo generation of
leukemogenic MCF virus in which replacement of ecotropic viral sequence
with endogenous information accounts for expanded host range and tissue
tropism.

Expression of the endogenous retroviral genes is controlled by two
distinct, mendelian loci, Gv-1 and Gv-2, requiring positive alleles at both
loci for expression of the multiple transcription units.  Transcription of
individual endogenous retroviral sequences is also independently regulated
at the tissue-specific level.  The coordinate regulation of endogenous
retroviral genes indicates that Gv-1 and Gv-2 encode a trans-acting factor
affecting the expression of multiple transcription units.

The mechanisms of this gene regulation will be examined in the congeneic
partner strains 129Gix+ and Gix-.  These strains bear positive alleles at
the Gv-2 locus but differ for alternative positive and negative alleles at
Gv-1.  The genomic DNA containing actively transcribed endogenous
retroviral genes will be isolated as recombinant DNA.  The cis-acting
elements which determine tissue-specific and genetic, Gv-1, responsiveness
will be analysed.  First, indirect assays of DNase 1 hypersensitive sites
in different tissues of Gix+ and Gix- mice will indicate possible binding
sites of proteins that confer gene regulation.  These studies will
distinguish between different transcription units by 5' unique flanking DNA
sequence.  Second direct analysis of the regulatory sequences will be
conducted by measuring the promotor activity in transient transfection
assays.  Progressive deletion and replacement experiments will locate the
position and orientation independent enhancer regions and factor binding
sites at the promotor.  Finally, strategies are described for identifying
and isolating the genetically defined Gv-1 regulatory locus.  These studies
will lead to further investigation to determine how the Gv-1 product
governs transcriptional activity in terms of protein structure and its
possible relationship to other eukaryote trans-acting regulatory factors.

## Key facts

- **NIH application ID:** 3171510
- **Project number:** 5R01CA033730-06
- **Recipient organization:** SCRIPPS CLINIC AND RESEARCH FOUNDATION
- **Principal Investigator:** MICHAEL COLIN WILSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $199,897
- **Award type:** 5
- **Project period:** 1983-05-01 → 1991-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171510

## Citation

> US National Institutes of Health, RePORTER application 3171510, REGULATION OF ENDOGENOUS RETROVIRAL GENE EXPRESSION (5R01CA033730-06). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171510. Licensed CC0.

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