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.
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