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Published on: August 29, 2020
Cdx2 represses Oct4 function via inducing its proteasome-dependent degradation in early porcine embryos
Gerelchimeg Bou1, Shichao Liu1, Jia Guo1
1College of Life Science, Northeast Agricultural University, Harbin 150030, China.
Abstract:
Reciprocal repression of inner cell mass specific factor OCT4 and trophectoderm specific factor CDX2 promotes mouse first lineage segregation. Studies in mouse embryonic stem (ES) cells revealed that they bind to each other's regulatory regions to reciprocally suppress transcription, additionally they form protein complex for mutual antagonism. However, so far the molecular interaction of Oct4 and Cdx2 in other mammal's early embryo is not yet investigated. Here, over-expression of Cdx2 in early porcine embryo showed CDX2 represses Oct4 through neither the transcriptional repression nor forming repressive complex, but promoting OCT4 nuclear export and proteasomal degradation. The results showed novel molecular regulation of CDX2 on Oct4, and provided important clues for clarifying the mechanism of interaction between CDX2 and Oct4 in embryo of mammals other than mouse.
Insights
In pigs, CDX2 represses OCT4 by promoting its export and degradation, unlike in mice. This finding reveals a novel mechanism for early embryonic lineage segregation in non-mouse mammals.
Area of Science:
- Developmental Biology
- Molecular Embryology
- Cell Biology
Background:
- OCT4 (octamer-binding transcription factor 4) and CDX2 (caudal-type homeobox 2) are key factors in mammalian early embryonic lineage segregation.
- In mice, OCT4 and CDX2 reciprocally repress each other transcriptionally and via protein complex formation.
- The molecular interaction between OCT4 and CDX2 in non-mouse mammals remains largely uninvestigated.
Purpose of the Study:
- To investigate the molecular mechanism by which CDX2 regulates OCT4 in early porcine embryos.
- To compare the interaction of OCT4 and CDX2 in porcine embryos with that observed in mouse embryos.
Main Methods:
- Overexpression of CDX2 in early porcine embryos.
- Analysis of OCT4 expression, localization, and degradation.
- Investigation of transcriptional repression and protein complex formation.
Main Results:
- CDX2 overexpression in porcine embryos did not lead to transcriptional repression of OCT4.
- CDX2 did not form a repressive protein complex with OCT4.
- CDX2 promoted the nuclear export and proteasomal degradation of OCT4 in porcine embryos.
Conclusions:
- CDX2 regulates OCT4 through a novel mechanism involving nuclear export and proteasomal degradation in porcine embryos.
- This mechanism differs from the reciprocal repression observed in mouse embryos.
- The findings provide crucial insights into the conserved and divergent mechanisms of early lineage segregation in mammals.
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