Mathematical Biology Seminar

Dean Tantin, U of U Pathology,
Wednesday, Dec. 1, 2021
3:05pm on Zoom
Transcriptional regulation of developmental lineage specification

Abstract: Preimplantation mammalian embryos contain cells capable of forming all subsequent organs and tissues of the organism. These ?pluripotent? cells maintain a large cohort of genes in a silent but poised state that allows for later expression. Depending on developmental lineage, subsets of these poised genes become activated later in development, while the remainder become stably repressed. The transcription factor Oct4 helps maintain these genes in a poised configuration, however Oct4 expression is lost prior to induction of these genes. We identify a related transcription factor with similar DNA binding site specificity, Oct1, as both co-expressed with Oct4 in pluripotent cells and maintained through differentiation. We show that differentiating cells lacking Oct1 induce lineage-appropriate genes poorly and aberrantly express lineage-inappropriate genes. The cells show ?fuzzy? gene expression patterns and proceed down incorrect developmental trajectories. Finally, we show that Oct1 associates with lineage-specific ?master regulator? transcription factors to mediate induction of lineage-appropriate developmental genes. These results suggest that Oct1 may be useful in optimizing developmental outcomes.