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Title: Dual Roles of Transcription Factor Zic3 in Regulating Embryonic Stem Cell Pluripotency and Differentiation
Keywords: Zic3, Sox2, transcription networks, embryonic stem cells
Issue Date: 20-Feb-2009
Source: LIM SHUSHAN LINDA (2009-02-20). Dual Roles of Transcription Factor Zic3 in Regulating Embryonic Stem Cell Pluripotency and Differentiation. ScholarBank@NUS Repository.
Abstract: The transcription factors Oct4, Nanog and Sox2 are key regulators of pluripotency and self-renewal in embryonic stem (ES) cells. I demonstrate that Zic3, a member of the Gli family of zinc finger transcription factors, is directly regulated by Oct4, Sox2, and Nanog. Knockdown of Zic3 expression in ES cells results in Nanog downregulation and induces the expression of endoderm lineage markers. This suggests that Zic3 prevents endodermal marker expression through Nanog-regulated pathways. I further identify the global targets of Zic3 in ES cells, including genes that are both related to pluripotency and lineage specification, and discuss their significance in my thesis. Finally, I present evidence for physical interaction between the Zic3 and Sox2 proteins and demonstrate that they share a significant overlap in target genes and common regulatory pathways. My work thus provides novel molecular insight into Zic3-regulated pathways that influence pluripotency and differentiation in ES cells.
Appears in Collections:Ph.D Theses (Open)

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