In:
Journal of Molecular Cell Biology, Oxford University Press (OUP)
Abstract:
The effective proliferation and differentiation of trophoblast stem cells (TSCs) is indispensable for the development of the placenta, which is the key to maintaining normal fetal growth during pregnancy. Kruppel-like factor 5 (Klf5) is implicated in the activation of pluripotent gene expression in embryonic stem cells (ESCs), yet its function in TSCs is poorly understood. Here, we show that Klf5 knockdown resulted in downregulation of core TSC-specific genes, consequently causing a rapid differentiation of TSCs. Consistently, Klf5-depleted embryos lost the ability to establish TSCs in vitro. At the molecular level, Klf5 preferentially occupied the proximal promoter regions and maintained an open chromatin architecture of key TSC-specific genes. Deprivation of Klf5 impaired the enrichment of p300, a major histone acetyl transferase of H3 lysine 27 acetylation (H3K27ac), and further decreased the occupancy of H3K27ac on promoters, leading to decreased transcriptional activity of TSC pluripotency-related genes. Thus, our findings highlight a novel mechanism of Klf5 in regulating the self-renewal and differentiation of TSCs, and provide a reference for understanding placental development and improving pregnancy rates.
Type of Medium:
Online Resource
ISSN:
1674-2788
,
1759-4685
DOI:
10.1093/jmcb/mjad045
Language:
English
Publisher:
Oxford University Press (OUP)
Publication Date:
2023
detail.hit.zdb_id:
2500949-7
SSG:
12
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