Zhong Deng

Abstract

The control of CD4 gene expression is essential for T lymphocyte development. Since the molecular mechanism for the control of CD4 gene expression during T cell development had not been elucidated, a study of the factors that control CD4 gene expression may lead to further. Toward these goals, we have made a series of recombinant DNA constructs to define the cis-acting transcriptional control elements in the murine CD4 locus that control CD4 gene expression during T cell development. In this study, we have identified multiple cis-acting control elements, which are critical for regulating the expression of the murine CD4 gene. Two intronic enhancers, which are located in a 122 bp Alul-Alul fragment 5' of the first intron and a 174 bp Pstl-SalI fragment 3' of the first intron, act in an orientation- and position-independent manner in both CD4+ and CD4- T cells. DNase I footprint analyses revealed the location of potential transcription factor-binding sequences in the protected regions include GATA-1, Elf-1, and AP-1 for the 5' intronic enhancer, and PU.1, IRF-1, and GATA-1 for the 3' intronic enhancer. Among them, Elf-1 and PU.1, members of the Ets protein family, and AP-1 have been implicated in the regulation of T cell-specific gene expression. An intronic promoter is located in the 138 bp fragment within the first intron. This promoter is activated preferentially in the CD4+CD8- T cells. Primer extension analysis indicates that the transcription initiation is located 107 bp upstream from the ATG site. A silencer element is loctaed in a 250 bp fragment corresponding to DH8, has a negative effect on the CD4 promoter activation in an orientation- and position-independent way in T cells. In summary, the molecular mechanisms, which control CD4 gene expression during T cell development, are complex and the result of coordinate interplay of multiple transcriptional control elements.

LLU Discipline

Biochemistry

Department

Biochemistry

School

Graduate School

First Advisor

Aladar A. Szalay

Second Advisor

Thomas Linkhart

Third Advisor

Charles W. Slattery

Fourth Advisor

Donna Strong

Fifth Advisor

R. Bruce Wilcox

Degree Name

Doctor of Philosophy (Medical Science)

Degree Level

Ph.D.

Year Degree Awarded

2000

Date (Title Page)

6-2000

Language

English

Library of Congress/MESH Subject Headings

Antigens -- immunology; Receptors, Antigen -- immunology; Antigens, CD4; Gene Expression Regulation, Developmental

Type

Dissertation

Page Count

xv; 210

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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