In this dissertation, I discovered that function of TRIM24 as a co-activator
of ERα-mediated transcriptional activation is dependent on specific histone
modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first
part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated
histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.
Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of
TRIM24-regulated ERα target genes is greatly impaired. Importantly, I
demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen
responsive elements (EREs) in a time-dependent manner upon estrogen
induction, and depletion of their expression exert corresponding time-dependent
effect on target gene activation. I also identified that phosphorylation of histone
H3 threonine T6 disrupts TRIM24 from binding to the chromatin and from
activating ERα-regulated targets. In the second part, I revealed that TRIM24
depletion has additive effect to LSD1 inhibitor- and Tamoxifen-mediated
reduction in survival and proliferation in breast cancer cells.
","abstract_html":"<p>In this dissertation, I discovered that function of TRIM24 as a co-activator</p> <p>of ERα-mediated transcriptional activation is dependent on specific histone</p> <p>modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first</p> <p>part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated</p> <p>histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.</p> <p>Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of</p> <p>TRIM24-regulated ERα target genes is greatly impaired. Importantly, I</p> <p>demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen</p> <p>responsive elements (EREs) in a time-dependent manner upon estrogen</p> <p>induction, and depletion of their expression exert corresponding time-dependent</p> <p>effect on target gene activation. I also identified that phosphorylation of histone</p> <p>H3 threonine T6 disrupts TRIM24 from binding to the chromatin and from</p> <p>activating ERα-regulated targets. In the second part, I revealed that TRIM24</p> <p>depletion has additive effect to LSD1 inhibitor- and Tamoxifen-mediated</p> <p>reduction in survival and proliferation in breast cancer cells.</p>","abstract_has_math":false,"creators":["Yiu, Teresa T"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Michelle Barton, Ph.D.","Gary Gallick, Ph.D.","Pierre McCrea, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2012,"date_issued":"2012-12-01T08:00:00Z","date_published":"2012-12-01T08:00:00Z","updated_at":"2026-07-24T05:48:59Z","subjects":["TRIM24","LSD1","H3K4 methylation","epigenetics","estrogen receptor","transcription","Biochemistry","Cancer Biology","Medicine and Health Sciences","Molecular Biology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/313","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Michelle Barton, Ph.D.","Gary Gallick, Ph.D.","Pierre McCrea, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Yiu, Teresa T"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.available","label":"Dc Date Available","values":["2012-12-04T08:00:00Z"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Dissertation (PhD)"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Doctor of Philosophy (PhD)"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["TRIM24","LSD1","H3K4 methylation","epigenetics","estrogen receptor","transcription","Biochemistry","Cancer Biology","Medicine and Health Sciences","Molecular Biology"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/313"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["In this dissertation, I discovered that function of TRIM24 as a co-activator
of ERα-mediated transcriptional activation is dependent on specific histone
modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first
part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated
histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.
Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of
TRIM24-regulated ERα target genes is greatly impaired. Importantly, I
demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen
responsive elements (EREs) in a time-dependent manner upon estrogen
induction, and depletion of their expression exert corresponding time-dependent
effect on target gene activation. I also identified that phosphorylation of histone
H3 threonine T6 disrupts TRIM24 from binding to the chromatin and from
activating ERα-regulated targets. In the second part, I revealed that TRIM24
depletion has additive effect to LSD1 inhibitor- and Tamoxifen-mediated
reduction in survival and proliferation in breast cancer cells.
"]},{"key":"dc:title","label":"Title","values":["Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells"]}]}],"canonical_facts":{"dc:contributor":["Michelle Barton, Ph.D.","Gary Gallick, Ph.D.","Pierre McCrea, Ph.D."],"dc:creator":["Yiu, Teresa T"],"dc:date.available":["2012-12-04T08:00:00Z"],"dc:description.abstract":["In this dissertation, I discovered that function of TRIM24 as a co-activator
of ERα-mediated transcriptional activation is dependent on specific histone
modifications in tumorigenic human breast cancer-derived MCF7 cells. In the first
part, I proved that TRIM24-PHD finger domain, which recognizes unmethylated
histone H3 lysine K4 (H3K4me0), is critical for ERα-regulated transcription.
Therefore, when LSD1-mediated demethylation of H3K4 is inhibited, activation of
TRIM24-regulated ERα target genes is greatly impaired. Importantly, I
demonstrated that TRIM24 and LSD1 are cyclically recruited to estrogen
responsive elements (EREs) in a time-dependent manner upon estrogen
induction, and depletion of their expression exert corresponding time-dependent
effect on target gene activation. I also identified that phosphorylation of histone
H3 threonine T6 disrupts TRIM24 from binding to the chromatin and from
activating ERα-regulated targets. In the second part, I revealed that TRIM24
depletion has additive effect to LSD1 inhibitor- and Tamoxifen-mediated
reduction in survival and proliferation in breast cancer cells.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/313"],"dc:subject":["TRIM24","LSD1","H3K4 methylation","epigenetics","estrogen receptor","transcription","Biochemistry","Cancer Biology","Medicine and Health Sciences","Molecular Biology"],"dc:title":["Trim24-Regulated Estrogen Response Is Dependent On Specific Histone Modifications In Breast Cancer Cells"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:48:59Z"}