Zfp281 shapes the transcriptome of trophoblast stem cells and is essential for placental development

Placental development is a key event in mammalian reproduction and embryogenesis. However, the molecular basis underlying extraembryonic lineage specification and subsequent placental development is not fully understood. Through a genetic screen, we identified Zfp281 as a key factor for extraembryonic development. Disruption of Zfp281 in mice caused severe defects in extraembryonic as well as embryonic tissues. Importantly, Zfp281 was preferentially expressed in the trophoblast stem cell population in an FGF-dependent manner and ensured the expression of genes necessary for placental development. Through the analysis of transcriptome and epigenome, we identified Zfp281 as an important factor to shape the transcriptome of mammalian trophoblast stem cells. Overall design: To study the role of Zfp281 in transcriptional regulation, we performed RNA-seq using mouse and human TS cells. Furthermore, we performed H3K4me3 ChIP-seq and ATAC-seq to reveal the roles of Zfp281 in chromatin regulation.

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Ishiuchi T, Ohishi H, Sato T, Kamimura S, Yorino M, Abe S, Suzuki A, Wakayama T, Suyama M, Sasaki H