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.
","abstract_html":"<p>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 <em>cis</em>-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 <em>cis</em>-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 <em>Alu</em>l-<em>Alu</em>l fragment 5' of the first intron and a 174 bp <em>Pst</em>l-<em>Sal</em>I fragment 3' of the first intron, act in an orientation- and position-independent manner in both CD4<sup>+</sup> and CD4<sup>-</sup> 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<sup>+</sup>CD8<sup>-</sup> 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.</p>","abstract_has_math":false,"creators":["Deng, Zhong"],"institution":null,"degree_name":"Doctor of Philosophy (Medical Science)","degree_level":"Dissertation","degree_discipline":"Biochemistry","degree_department":null,"school":null,"contributors":["Aladar A. Szalay","Thomas Linkhart","Charles W. Slattery","Donna Strong","R. Bruce Wilcox"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2000,"date_issued":"2000-06-01T07:00:00Z","date_published":"2000-06-01T07:00:00Z","updated_at":"2026-07-24T02:53:44Z","subjects":["Biochemistry","Genetic Structures","Laboratory and Basic Science Research","Antigens -- immunology; Receptors, Antigen -- immunology; Antigens, CD4; Gene Expression Regulation, Developmental"],"languages":["English"],"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."],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarsrepository.llu.edu/etd/1411","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Aladar A. Szalay","Thomas Linkhart","Charles W. Slattery","Donna Strong","R. Bruce Wilcox"]},{"key":"dc:creator","label":"Author","values":["Deng, Zhong"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"thesis:degree_discipline","label":"Discipline","values":["Biochemistry"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (Medical Science)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biochemistry","Genetic Structures","Laboratory and Basic Science Research","Antigens -- immunology; Receptors, Antigen -- immunology; Antigens, CD4; Gene Expression Regulation, Developmental"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["English"]},{"key":"dc:rights","label":"Dc Rights","values":["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."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://scholarsrepository.llu.edu/etd/1411"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["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.
"]},{"key":"dc:title","label":"Title","values":["Identification and Characterization of Control Elements within the Murine CD4 Gene"]}]}],"canonical_facts":{"dc:contributor":["Aladar A. Szalay","Thomas Linkhart","Charles W. Slattery","Donna Strong","R. Bruce Wilcox"],"dc:creator":["Deng, Zhong"],"dc:description.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.
"],"dc:identifier":["https://scholarsrepository.llu.edu/etd/1411"],"dc:language":["English"],"dc: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."],"dc:subject":["Biochemistry","Genetic Structures","Laboratory and Basic Science Research","Antigens -- immunology; Receptors, Antigen -- immunology; Antigens, CD4; Gene Expression Regulation, Developmental"],"dc:title":["Identification and Characterization of Control Elements within the Murine CD4 Gene"],"thesis:degree_discipline":["Biochemistry"],"thesis:degree_level":["Dissertation"],"thesis:degree_name":["Doctor of Philosophy (Medical Science)"]},"updated_at":"2026-07-24T02:53:44Z"}