# REGULATION OF CHORIONIC GONADOTROPIN GENE EXPRESSION

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 1994 · $162,815

## Abstract

Chorionic gonadotropin (CG) is a placental hormone that stimulates
steroidogenesis in the corpus luteum, providing an essential step in
the maintenance of early pregnancy.  Because it is expressed at high
levels within days after fertilization and implantation, CG is used
routinely to detect pregnancy at early stages and to monitor the
progress of pregnancy during the first trimester.  CG is also produced
in a variety of different malignancies, and it is used as a tumor
marker in these conditions.  CG is a heterodimeric hormone that is
encoded by separate alpha and beta subunit genes.  The current proposal
will focus on transcriptional control of the CGbeta subunit genes.
There are six separate CGbeta genes that arose by gene duplication from
an ancestral luteinizing hormone (LHbeta) gene.  In the course of
evolution, several of the CGbeta genes acquired unique regulatory
sequences that dictate expression from a new upstream promoter site and
thereby confer gene expression in the placenta rather than in the
pituitary.  The CGbeta gene also provides a model for understanding new
pathways of transcriptional regulation by cAMP.  We propose an
integrated series of studies to identify regulatory DNA elements in the
CGbeta promoter and to use these sequences as tools to identify
transcription factors that regulate tissue-specific and cAMP-mediated
expression of the CGbeta gene.  The five specific aims are to:  1)
Determine the functional properties of the six different CGbeta genes
in vivo and in transfected cells.  Identification of the functional and
nonfunctional members of the CGbeta gene family provides a foundation
for subsequent studies to elucidate the promoter sequences that are
essential for CGbeta gene expression in the placenta; 2) Determine
whether enhancer elements reside outside of 5'-flanking regions of the
CGbeta genes.  The CGbeta/LHbeta gene cluster will be analyzed using
DNase I hypersensitivity and screened for intragenic and downstream
enhancer elements that can activate expression of a minimal CGbeta
promoter.  3) Define the base substitutions in the active CGbeta genes
that confer placenta specific expression.  Based upon comparisons of
functional and nonfunctional promoter sequences, site-directed
mutagenesis will be used to determine which of the relatively small
number of nucleotide differences account for activation of the CGbeta
promoter in placental cells; 4) Define, using site-directed
mutagenesis, the sequence determinants of a novel cAMP response element
(CRE) in the CGbeta promoter; 5) Identify and characterize the
transcription factor(s) that binds to a repeated functional motif in
the CGbeta CRE.  Labeled CGbeta sequences will be used in an expression
cloning strategy to identify a transcription factor that binds
specifically to the CGbeta CRE.  After cloning the transcription
factor, patterns of expression will be analyzed in different tissues
and during development and its functional properties will be examined
in ...

## Key facts

- **NIH application ID:** 2198894
- **Project number:** 5R01HD023519-07
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **SAM.gov UEI:** KG76WYENL5K1
- **Principal Investigator:** James Larry JAMESON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $162,815
- **Award type:** 5
- **Project period:** 1988-08-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2198894

## Citation

> US National Institutes of Health, RePORTER application 2198894, REGULATION OF CHORIONIC GONADOTROPIN GENE EXPRESSION (5R01HD023519-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2198894. Licensed CC0.

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