SETD3-dependent gene expression changes during endoderm differentiation of mouse embryonic stem cells

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2022-2-09
Balbaşı, Emre
Mouse embryonic stem cells (mESCs) are pluripotent cells that have self renewal capability. They can differentiate into all three primary germ layers: mesoderm, endoderm, and ectoderm during embryonic development. The embryonic development is controlled via spatiotemporal regulation of gene expression changes. The collaborative effects of Wnt, Nodal, BMP signaling pathways help form the primitive streak, and the subsequent definitive endoderm layer in the gastrulating embryo. Deactivation of core pluripotency network, and activation of germ layer specific transcription netwoks are required for this process. This is precisely achieved by chromatin-based regulation. SETD3 is a SET-domain containing methyltransferase that targets both histone and nonhistone proteins. An shRNA screen identified SETD3 as a key factor for mesendoderm commitment of mESCs. Setd3 knock-out mESC cannot upregulate pioneer transcription factors that initiate mesendoderm differentiation in vitro. In this project, we aimed to determine SETD3- dependent gene expression changes during the endoderm differentiation of mouse embyronic stem cells (mESCs) and we performed time-course endoderm differentiation experiments and employed RNA-sequencing to identify differentially expressed genes (DEGs) in the absence of SETD3. Our results indicate a role for SETD3 in timely downregulation of the pluripotent state, and response to key signaling pathways which leads to the delayed and defective differentiation in its absence.

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Citation Formats
E. Balbaşı, “SETD3-dependent gene expression changes during endoderm differentiation of mouse embryonic stem cells,” M.S. - Master of Science, Middle East Technical University, 2022.