{"id":{"repo_id":"ku","oai_identifier":"oai:kuscholarworks.ku.edu:1808/12175"},"canonical_url":"https://search.dev.ndltd.org/etd/ku/oai:kuscholarworks.ku.edu:1808/12175","repository":{"repo_id":"ku","name":"University of Kansas","base_url":"https://kuscholarworks.ku.edu/server/oai/request"},"display":{"title":"THE APPLICATION OF HISTONE ANALYSIS FOR IDENTIFYING DISTAL REGULATORY ELEMENTS - REGULATION OF FSHR","abstract":"Mechanisms that regulate gene expression are fundamental to many complex biological processes and disease states. Genome-wide approaches that combine chromatin-immunoprecipitation (ChIP) and next-generation sequencing have greatly advanced our understanding of chromatin structure and the role that histone modification plays in transcriptional regulation. In particular, these advances revealed important associations between functional, non-coding DNAs and specific histone modifications, which have been used technically to identify numerous distal regulatory elements and furthered our knowledge of transcriptional regulation and cell-specific gene regulation. Fshr is a gene expressed only in testicular Sertoli cells and ovarian granulosa cells and its expression is critical for proper gonad function and fertility. Importantly, underlying its exquisite cell-specificity is a transcriptional mechanism limited to only two cell types, which previous studies revealed was dependent on distal regulatory elements. To help identify these elements, we used ChIP, combined with next-generation sequencing, to globally map Histone 3 Lysine 4 tri-methylation (H3K4me3) in Sertoli and myoid cells. H3K4me3 is a post-translational histone modification known to associate with distal regulatory elements and promoter regions of actively transcribed genes. Analysis of H3K4me3 enrichment profiles identified a distal site 3' to Fshr that was specific to Sertoli cells. Transient transfection analysis indicated the region represses Fshr promoter activity and in vitro binding analysis revealed that GATA-4 and an unknown protein bound to the region, implicating them in cell-specific regulation of Fshr. These studies provide evidence that Fshr is regulated by a distal regulatory element and have provided insight into the nature of these regulatory proteins. This work provides a database mapping H3K4me3 enrichment within Sertoli and peritubular myoid cells that can be used to identify new regulatory regions. Overall, these studies have furthered our knowledge of cell-specific gene regulation in Sertoli cells and provided new data that will lead to a better understanding of transcriptional regulation in Sertoli cells.","abstract_html":"Mechanisms that regulate gene expression are fundamental to many complex biological processes and disease states. Genome-wide approaches that combine chromatin-immunoprecipitation (ChIP) and next-generation sequencing have greatly advanced our understanding of chromatin structure and the role that histone modification plays in transcriptional regulation. In particular, these advances revealed important associations between functional, non-coding DNAs and specific histone modifications, which have been used technically to identify numerous distal regulatory elements and furthered our knowledge of transcriptional regulation and cell-specific gene regulation. Fshr is a gene expressed only in testicular Sertoli cells and ovarian granulosa cells and its expression is critical for proper gonad function and fertility. Importantly, underlying its exquisite cell-specificity is a transcriptional mechanism limited to only two cell types, which previous studies revealed was dependent on distal regulatory elements. To help identify these elements, we used ChIP, combined with next-generation sequencing, to globally map Histone 3 Lysine 4 tri-methylation (H3K4me3) in Sertoli and myoid cells. H3K4me3 is a post-translational histone modification known to associate with distal regulatory elements and promoter regions of actively transcribed genes. Analysis of H3K4me3 enrichment profiles identified a distal site 3' to Fshr that was specific to Sertoli cells. Transient transfection analysis indicated the region represses Fshr promoter activity and in vitro binding analysis revealed that GATA-4 and an unknown protein bound to the region, implicating them in cell-specific regulation of Fshr. These studies provide evidence that Fshr is regulated by a distal regulatory element and have provided insight into the nature of these regulatory proteins. This work provides a database mapping H3K4me3 enrichment within Sertoli and peritubular myoid cells that can be used to identify new regulatory regions. Overall, these studies have furthered our knowledge of cell-specific gene regulation in Sertoli cells and provided new data that will lead to a better understanding of transcriptional regulation in Sertoli cells.","abstract_has_math":false,"creators":["Dille, Elizabeth A."],"institution":"University of Kansas","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Heckert, Leslie L"],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-05-31","date_published":"2013-05-31","updated_at":"2026-07-24T02:47:03Z","subjects":["Biology","Endocrinology","Genetics","Distal regulatory elements","Fshr","Sertoli cells"],"languages":["en"],"rights":["This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author."],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:12722"],"render_values":[{"text":"http://dissertations.umi.com/ku:12722","href":"http://dissertations.umi.com/ku:12722","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/1808/12175","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Heckert, Leslie L"]},{"key":"dc:creator","label":"Author","values":["Dille, Elizabeth A."]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2013-09-29T13:49:30Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2013-09-29T13:49:30Z"]},{"key":"dc:date.issued","label":"Date","values":["2013-05-31"]},{"key":"dc:publisher","label":"Institution","values":["University of Kansas"]},{"key":"dc:type","label":"Dc Type","values":["Dissertation"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Biology","Endocrinology","Genetics","Distal regulatory elements","Fshr","Sertoli cells"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]},{"key":"dc:rights","label":"Dc Rights","values":["This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["http://dissertations.umi.com/ku:12722"]},{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/1808/12175"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Mechanisms that regulate gene expression are fundamental to many complex biological processes and disease states. Genome-wide approaches that combine chromatin-immunoprecipitation (ChIP) and next-generation sequencing have greatly advanced our understanding of chromatin structure and the role that histone modification plays in transcriptional regulation. In particular, these advances revealed important associations between functional, non-coding DNAs and specific histone modifications, which have been used technically to identify numerous distal regulatory elements and furthered our knowledge of transcriptional regulation and cell-specific gene regulation. Fshr is a gene expressed only in testicular Sertoli cells and ovarian granulosa cells and its expression is critical for proper gonad function and fertility. Importantly, underlying its exquisite cell-specificity is a transcriptional mechanism limited to only two cell types, which previous studies revealed was dependent on distal regulatory elements. To help identify these elements, we used ChIP, combined with next-generation sequencing, to globally map Histone 3 Lysine 4 tri-methylation (H3K4me3) in Sertoli and myoid cells. H3K4me3 is a post-translational histone modification known to associate with distal regulatory elements and promoter regions of actively transcribed genes. Analysis of H3K4me3 enrichment profiles identified a distal site 3' to Fshr that was specific to Sertoli cells. Transient transfection analysis indicated the region represses Fshr promoter activity and in vitro binding analysis revealed that GATA-4 and an unknown protein bound to the region, implicating them in cell-specific regulation of Fshr. These studies provide evidence that Fshr is regulated by a distal regulatory element and have provided insight into the nature of these regulatory proteins. This work provides a database mapping H3K4me3 enrichment within Sertoli and peritubular myoid cells that can be used to identify new regulatory regions. Overall, these studies have furthered our knowledge of cell-specific gene regulation in Sertoli cells and provided new data that will lead to a better understanding of transcriptional regulation in Sertoli cells."]},{"key":"dc:title","label":"Title","values":["THE APPLICATION OF HISTONE ANALYSIS FOR IDENTIFYING DISTAL REGULATORY ELEMENTS - REGULATION OF FSHR"]}]}],"canonical_facts":{"dc:contributor.advisor":["Heckert, Leslie L"],"dc:creator":["Dille, Elizabeth A."],"dc:date.accessioned":["2013-09-29T13:49:30Z"],"dc:date.available":["2013-09-29T13:49:30Z"],"dc:date.issued":["2013-05-31"],"dc:description.abstract":["Mechanisms that regulate gene expression are fundamental to many complex biological processes and disease states. Genome-wide approaches that combine chromatin-immunoprecipitation (ChIP) and next-generation sequencing have greatly advanced our understanding of chromatin structure and the role that histone modification plays in transcriptional regulation. In particular, these advances revealed important associations between functional, non-coding DNAs and specific histone modifications, which have been used technically to identify numerous distal regulatory elements and furthered our knowledge of transcriptional regulation and cell-specific gene regulation. Fshr is a gene expressed only in testicular Sertoli cells and ovarian granulosa cells and its expression is critical for proper gonad function and fertility. Importantly, underlying its exquisite cell-specificity is a transcriptional mechanism limited to only two cell types, which previous studies revealed was dependent on distal regulatory elements. To help identify these elements, we used ChIP, combined with next-generation sequencing, to globally map Histone 3 Lysine 4 tri-methylation (H3K4me3) in Sertoli and myoid cells. H3K4me3 is a post-translational histone modification known to associate with distal regulatory elements and promoter regions of actively transcribed genes. Analysis of H3K4me3 enrichment profiles identified a distal site 3' to Fshr that was specific to Sertoli cells. Transient transfection analysis indicated the region represses Fshr promoter activity and in vitro binding analysis revealed that GATA-4 and an unknown protein bound to the region, implicating them in cell-specific regulation of Fshr. These studies provide evidence that Fshr is regulated by a distal regulatory element and have provided insight into the nature of these regulatory proteins. This work provides a database mapping H3K4me3 enrichment within Sertoli and peritubular myoid cells that can be used to identify new regulatory regions. Overall, these studies have furthered our knowledge of cell-specific gene regulation in Sertoli cells and provided new data that will lead to a better understanding of transcriptional regulation in Sertoli cells."],"dc:identifier.other":["http://dissertations.umi.com/ku:12722"],"dc:identifier.uri":["http://hdl.handle.net/1808/12175"],"dc:language.iso":["en"],"dc:publisher":["University of Kansas"],"dc:rights":["This item is protected by copyright and unless otherwise specified the copyright of this thesis/dissertation is held by the author."],"dc:subject":["Biology","Endocrinology","Genetics","Distal regulatory elements","Fshr","Sertoli cells"],"dc:title":["THE APPLICATION OF HISTONE ANALYSIS FOR IDENTIFYING DISTAL REGULATORY ELEMENTS - REGULATION OF FSHR"],"dc:type":["Dissertation"]},"updated_at":"2026-07-24T02:47:03Z"}