Super-enhancer-guided mapping of regulatory networks controlling mouse trophoblast stem cells

Bum-Kyu Lee, Yu jin Jang, Mijeong Kim, Lucy LeBlanc, Catherine Rhee, Jiwoon Lee, Samuel Beck, Wenwen Shen and Jonghwan Kim ()
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Bum-Kyu Lee: The University of Texas at Austin
Yu jin Jang: The University of Texas at Austin
Mijeong Kim: The University of Texas at Austin
Lucy LeBlanc: The University of Texas at Austin
Catherine Rhee: The University of Texas at Austin
Jiwoon Lee: The University of Texas at Austin
Samuel Beck: The University of Texas at Austin
Wenwen Shen: The University of Texas at Austin
Jonghwan Kim: The University of Texas at Austin

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract Trophectoderm (TE) lineage development is pivotal for proper implantation, placentation, and healthy pregnancy. However, only a few TE-specific transcription factors (TFs) have been systematically characterized, hindering our understanding of the process. To elucidate regulatory mechanisms underlying TE development, here we map super-enhancers (SEs) in trophoblast stem cells (TSCs) as a model. We find both prominent TE-specific master TFs (Cdx2, Gata3, and Tead4), and >150 TFs that had not been previously implicated in TE lineage, that are SE-associated. Mapping targets of 27 SE-predicted TFs reveals a highly intertwined transcriptional regulatory circuitry. Intriguingly, SE-predicted TFs show 4 distinct expression patterns with dynamic alterations of their targets during TSC differentiation. Furthermore, depletion of a subset of TFs results in dysregulation of the markers for specialized cell types in placenta, suggesting a role during TE differentiation. Collectively, we characterize an expanded TE-specific regulatory network, providing a framework for understanding TE lineage development and placentation.

Date: 2019
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12720-6

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DOI: 10.1038/s41467-019-12720-6

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