Abstract

CD4 is a membrane bound glycoprotein that plays an important role in T cell development and activation. An extensive analysis of the CD4 locus identified potential transcriptional control elements located 5' of the promoter and within the first intron. Since the molecular mechanism for the control of CD4 expression during T cell development had not been determined, it is the focus of this dissertation. A series of recombinant DNA constructs were made to determine the contribution of putative transcriptional control elements in regard to CD4 expression, and to identify elements being used to control CD4 expression during T cell development. One of these control elements, located within the first intron, was further characterized to determine the DNA sequence involved. In addition, the 15 kb 5' of the promoter and the 9 kb first intron were sequenced and analyzed for homology to previously identified control elements. Our results indicate that there are multiple cis-acting elements which control the expression of the murine CD4 gene. Elements that have a positive effect on the expression of the CD4 gene are located: (1) about 13.5 kb 5' of the first exon; and (2) within the first intron. Elements that have a negative effect on the expression of the CD4 gene are located: (1) near the 5' enhancer; (2) between the promoter and 5' enhancer; (3) within the first intron about 2.5 kb 3' of the promoter; and (4) within the first intron about 4 kb 3' of the promoter. In addition, the enhancer located 13.5 kb 5' of the promoter stimulates transcription from the CD4 promoter when the enhancer is left in it’s native context as long as some of the intervening DNA sequence is deleted. The negative element located within the first intron about 4 kb 3' of the promoter corresponds to a GATA repeat. Sequence analysis of the DNA regions containing these positive and negative elements indicates regions of DNA that could be responsible for the functional activity associated with particular regions.

LLU Discipline

Microbiology and Molecular Genetics

School

Graduate School

First Advisor

John F. Sands

Second Advisor

Wendy Haggren

Third Advisor

Ellen V. Rothenberg

Fourth Advisor

Donna D. Stong

Fifth Advisor

Barry L. Taylor

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

1995

Date (Title Page)

8-1995

Language

English

Library of Congress/MESH Subject Headings

Genetics, Biochemical; Antigens, CD4; Antigens, CD8; CD4-CD8 Ratio; Genetic Vectors; Gene Expression Regulation, Developmental

Type

Dissertation

Page Count

xviii; 289

Digital Format

PDF

Digital Publisher

Loma Linda University Libraries

Usage Rights

This title appears here courtesy of the author, who has granted Loma Linda University a limited, non-exclusive right to make this publication available to the public. The author retains all other copyrights.

Collection

Loma Linda University Electronic Theses and Dissertations

Collection Website

http://scholarsrepository.llu.edu/etd/

Repository

Loma Linda University. Del E. Webb Memorial Library. University Archives

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