PhD Transfer Seminar – Mario Filice (Mitchell Lab)

Characterizing Cis-Regulatory Elements Responsible for Regulating Sfmbt2 & Trophectoderm Specific Enhancers 

Abstract

Extraembryonic development is arguably as important as embryonic development, as defects in placental development can lead to lifelong deficiencies or even fetal death. There is a large gap in information regarding the transcriptional regulatory network that operates within these extraembryonic tissues, as they are usually overshadowed by investigations in embryonic tissues. Extraembryonic development starts with Trophoblast Stem Cells (TSC), the extraembryonic progenitor cells which go on to form all the different cell types that create the placenta. TSCs have their own unique repertoire of transcription factors that act at cell-type specific enhancers which in turn regulate TSC specific genes. The expression of these genes allows TSCs to self-replicate and differentiate into all placental cell-types. Specifically, a critical, imprinted TSC gene Sfmbt2, is required for TSC maintenance in vivo, however, we lack information on how the expression of this gene is regulated. I hypothesize that an upstream enhancer we determined contacts the expressed allele in TSCs, using allele specific e4C chromatin capture, is responsible for regulating Sfmbt2 expression, and activity of this region is governed by TSC specific transcription factors. I also hypothesize that this region is responsible for reactivating the normally silent maternal allele when the paternal, expressed allele is deleted. Additionally, I aim to identify regions conserved across different species, with conserved chromatin features that identify enhancers. I will also investigate what individual components of enhancers that are responsible for conferring cell-type specific activity in similar, yet distinct cell-types. By understanding the building blocks that make up cell-type specific enhancers, active in these two different early developmental lineages (Embryonic Stem Cells and Trophoblast Stem Cells), I will define the TSC regulatory network and identify sequences required for gene regulation during early development.

https://utoronto.zoom.us/j/81645322266

Meeting ID: 816 4532 2266
Host: Jennifer Mitchell (ja.mitchell@utoronto.ca)