First Advisor

Robert L. Millette

Term of Graduation

Fall 1995

Date of Publication


Document Type


Degree Name

Master of Science (M.S.) in Biology






Nucleotide sequence, Genetic regulation, Herpes simplex virus



Physical Description

1 online resource (ii, 53 pages)


The human c-myc gene is a cellular proto-oncogene composed of three exons and two introns. Transcription of c-myc is controlled by two promoters, P1 and P2. The activity of these promoters is regulated by many factors, such as cellular transcription factors E2F, YY1, and HSV-1 immediate-early proteins, ICP0, ICP4.

Many regulatory elements located both upstream of and between P1 and P2 have been identified, and some of these are required for optimum expression of c-myc. In this thesis research, a region downstream from P2 in the c-myc exon 1 was identified by its response to transactivation by HSV-1 immediate-early proteins, ICP0 and ICP4. The purpose of this research was to examine this region for regulatory sites that respond to HSV-1 infection. I hypothesized that after HSV-1 infection, ICP0 and ICP4 activate c-myc expression, in part, through regulatory sequences present in exon 1.

To test for this hypothesis, reporter plasmids containing (I) the c-myc promoter (from - 101 bp relative to P1) and exon 1 coupled to the bacterial CAT gene were constructed. (ii) The c-myc exon sequences used were either intact (wild-type) or they were constructed with various deletions. The activities of these plasmids were examined in transient expression assays. To analyze protein binding, electrophoretic mobility shift assay (EMSA) and completion EMSAs were carried out. The results from these experiments lead to the following conclusions: (i) ICP4 and ICP0 serve as activators, whereas ICP27 inhibits c-myc gene expression. (ii) The region from +332 to +513 within the c-myc exon 1 contains an important element required for transactivation of the c-myc gene by HSV-1 proteins. (iii) Cellular proteins, including factor YY1, bind to the region from +332 to +513 in the c-myc exon 1.

Although the exact mechanism by which HSV-1 immediate-early proteins regulate c-myc gene expression is still not clear, it gives rise to a possibility that this regulation is caused by turning on or activation of the cellular regulatory proteins by ICP4 and ICP0. The cellular proteins in turn activate the c-myc gene expression by interacting with the ciselement downstream from P2.


In Copyright. URI: This Item is protected by copyright and/or related rights. You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).


If you are the rightful copyright holder of this dissertation or thesis and wish to have it removed from the Open Access Collection, please submit a request to and include clear identification of the work, preferably with URL.

Persistent Identifier

Included in

Biology Commons