scholarly journals Nr0b1 is a negative regulator of Zscan4c in mouse embryonic stem cells

2015 ◽  
Vol 5 (1) ◽  
Author(s):  
Setsuko Fujii ◽  
Satomi Nishikawa-Torikai ◽  
Yoko Futatsugi ◽  
Yayoi Toyooka ◽  
Mariko Yamane ◽  
...  
2019 ◽  
Author(s):  
Fabrice Gonnot ◽  
Diana Langer ◽  
Pierre-Yves Bourillot ◽  
Nathalie Doerflinger ◽  
Pierre Savatier

AbstractContinuous, non-cell cycle-dependent expression of cyclin E is a characteristic feature of mouse embryonic stem cells (ESCs). We studied the 5’ regulatory region of Cyclin E, also known as Ccne1, and identified binding sites for transcription factors of the naïve pluripotency network, including Esrrb, Klf4, and Tfcp2l1 within 1 kilobase upstream of the transcription start site. Luciferase assay and chromatin immunoprecipitation-quantitative polymerase chain reaction (ChiP–qPCR) study highlighted one binding site for Esrrb that is essential to transcriptional activity of the promoter region, and three binding sites for Klf4 and Tfcp2l1. Knockdown of Esrrb, Klf4, and Tfcp2l1 reduced Cyclin E expression whereas overexpression of Esrrb and Klf4 increased it, indicating a strong correlation between the expression level of these factors and that of cyclin E. We observed that cyclin E overexpression delays differentiation induced by Esrrb depletion, suggesting that cyclin E is an important target of Esrrb for differentiation blockade. We observed that mESCs express a low level of miR-15a and that transfection of a miR-15a mimic decreases Cyclin E mRNA level. These results lead to the conclusion that the high expression level of Cyclin E in mESCs can be attributed to transcriptional activation by Esrrb as well as to the absence of its negative regulator, miR-15a.


2021 ◽  
Author(s):  
Deepika Puri ◽  
Birgit Koschorz ◽  
Bettina Engist ◽  
Megumi Onishi-Seebacher ◽  
Devon Ryan ◽  
...  

Repeat element transcription plays a vital role in early embryonic development. Expression of repeats such as MERVL characterises mouse embryos at the 2-cell stage, and defines a 2-cell-like cell (2CLC) population in a mouse embryonic stem cell culture. Repeat element sequences contain binding sites for numerous transcription factors. We identify the forkhead domain transcription factor FOXD3 as a regulator of repeat element transcription in mouse embryonic stem cells. FOXD3 binds to and recruits the histone methyltransferase SUV39H1 to MERVL and major satellite repeats, consequentially repressing the transcription of these repeats by the establishment of the H3K9me3 heterochromatin modification. Notably, depletion of FOXD3 leads to the de-repression of MERVL and major satellite repeats as well as a subset of genes expressed in the 2-cell state, shifting the balance between the stem cell and 2 cell-like population in culture. Thus, FOXD3 acts as a negative regulator of repeat transcription, ascribing a novel function to this transcription factor.


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