Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo.
In this dissertation project, we use a murine ESC aggregation assay (embryoid body formation, EB) to model the early development stages that proceed gastrulation, and report that GCN5, a histone acetyltransferase (HAT) essential for embryonic development, is required for proper expression of multiple genes encoding components of the FGF signaling pathway, and for normal activation of ERK and p38 downstream of FGF signaling at early stages of EB formation. Loss of Gcn5 is associated with disorganized cytoskeletal networks, and compromised capacity of ESCs to differentiate toward mesodermal and endodermal lineages. We identified 7 genes as putative direct targets of GCN5 during early differentiation by using RNAseq and H3K9ac ChIPseq. These genes are reportedly involved in signaling and metabolism, and most interestingly, 4 of them are c-MYC targets. These findings established a novel link between GCN5 and FGF signaling pathway, and highlighted the GCN5-MYC partnership in gene regulation during early differentiation.
","abstract_html":"<p>Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages <em>in vitro</em> that parallel developmental events during embryogenesis <em>in vivo</em>.</p> <p>In this dissertation project, we use a murine ESC aggregation assay (embryoid body formation, EB) to model the early development stages that proceed gastrulation, and report that GCN5, a histone acetyltransferase (HAT) essential for embryonic development, is required for proper expression of multiple genes encoding components of the FGF signaling pathway, and for normal activation of ERK and p38 downstream of FGF signaling at early stages of EB formation. Loss of <em>Gcn5</em> is associated with disorganized cytoskeletal networks, and compromised capacity of ESCs to differentiate toward mesodermal and endodermal lineages. We identified 7 genes as putative direct targets of GCN5 during early differentiation by using RNAseq and H3K9ac ChIPseq. These genes are reportedly involved in signaling and metabolism, and most interestingly, 4 of them are c-MYC targets. These findings established a novel link between GCN5 and FGF signaling pathway, and highlighted the GCN5-MYC partnership in gene regulation during early differentiation.</p>","abstract_has_math":false,"creators":["Wang, Li","0000-0003-0029-1920
"],"institution":null,"degree_name":"Doctor of Philosophy (PhD)","degree_level":"Dissertation (PhD)","degree_discipline":null,"degree_department":null,"school":null,"contributors":["Sharon Y. R. Dent, Ph.D.","Mark T. Bedford, Ph.D.","David G. Johnson, Ph.D."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017-08-01T07:00:00Z","date_published":"2017-08-01T07:00:00Z","updated_at":"2026-07-24T05:50:02Z","subjects":["Gcn5","FGF signaling","Myc","Emrbyoid body","Chromatin","Histone H3","Acetylation","Biological Factors","Cell Biology","Developmental Biology","Medicine and Health Sciences","Molecular Biology"],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://digitalcommons.library.tmc.edu/utgsbs_dissertations/799","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Sharon Y. R. Dent, Ph.D.","Mark T. Bedford, Ph.D.","David G. Johnson, Ph.D."]},{"key":"dc:creator","label":"Author","values":["Wang, Li","0000-0003-0029-1920
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In this dissertation project, we use a murine ESC aggregation assay (embryoid body formation, EB) to model the early development stages that proceed gastrulation, and report that GCN5, a histone acetyltransferase (HAT) essential for embryonic development, is required for proper expression of multiple genes encoding components of the FGF signaling pathway, and for normal activation of ERK and p38 downstream of FGF signaling at early stages of EB formation. Loss of Gcn5 is associated with disorganized cytoskeletal networks, and compromised capacity of ESCs to differentiate toward mesodermal and endodermal lineages. We identified 7 genes as putative direct targets of GCN5 during early differentiation by using RNAseq and H3K9ac ChIPseq. These genes are reportedly involved in signaling and metabolism, and most interestingly, 4 of them are c-MYC targets. These findings established a novel link between GCN5 and FGF signaling pathway, and highlighted the GCN5-MYC partnership in gene regulation during early differentiation.
"]},{"key":"dc:title","label":"Title","values":["Gcn5 Impacts Fgf Signaling At Multiple Levels and Activates C-Myc Target Genes During Early Differentiation of Embryoid Bodies"]}]}],"canonical_facts":{"dc:contributor":["Sharon Y. R. Dent, Ph.D.","Mark T. Bedford, Ph.D.","David G. Johnson, Ph.D."],"dc:creator":["Wang, Li","0000-0003-0029-1920
"],"dc:date.available":["2018-02-12T08:00:00Z"],"dc:description.abstract":["Precise control of gene expression during development is orchestrated by transcription factors, signaling pathways and co-regulators, with complex cross-regulatory events often occurring. Growing evidence has identified chromatin modifiers as important regulators for development as well, yet how particular chromatin modifying enzymes affect specific developmental processes remains largely unclear. Embryonic stem cells (ESCs) are self-renewing, pluripotent, and have the abilities to generate almost all cell types in adult tissues. The dual capacity of ESCs to self-renew and differentiate offers unlimited potential for studying gene regulation events at specific developmental stages in vitro that parallel developmental events during embryogenesis in vivo.
In this dissertation project, we use a murine ESC aggregation assay (embryoid body formation, EB) to model the early development stages that proceed gastrulation, and report that GCN5, a histone acetyltransferase (HAT) essential for embryonic development, is required for proper expression of multiple genes encoding components of the FGF signaling pathway, and for normal activation of ERK and p38 downstream of FGF signaling at early stages of EB formation. Loss of Gcn5 is associated with disorganized cytoskeletal networks, and compromised capacity of ESCs to differentiate toward mesodermal and endodermal lineages. We identified 7 genes as putative direct targets of GCN5 during early differentiation by using RNAseq and H3K9ac ChIPseq. These genes are reportedly involved in signaling and metabolism, and most interestingly, 4 of them are c-MYC targets. These findings established a novel link between GCN5 and FGF signaling pathway, and highlighted the GCN5-MYC partnership in gene regulation during early differentiation.
"],"dc:identifier":["https://digitalcommons.library.tmc.edu/utgsbs_dissertations/799"],"dc:subject":["Gcn5","FGF signaling","Myc","Emrbyoid body","Chromatin","Histone H3","Acetylation","Biological Factors","Cell Biology","Developmental Biology","Medicine and Health Sciences","Molecular Biology"],"dc:title":["Gcn5 Impacts Fgf Signaling At Multiple Levels and Activates C-Myc Target Genes During Early Differentiation of Embryoid Bodies"],"thesis:degree_level":["Dissertation (PhD)"],"thesis:degree_name":["Doctor of Philosophy (PhD)"]},"updated_at":"2026-07-24T05:50:02Z"}