scholarly journals The combined action of Esrrb and Nr5a2 is essential for murine naïve pluripotency.

Development ◽  
2021 ◽  
Author(s):  
Nicola Festuccia ◽  
Nick Owens ◽  
Almira Chervova ◽  
Agnès Dubois ◽  
Pablo Navarro

The maintenance of pluripotency in mouse embryonic stem cells (ESCs) is governed by the action of an interconnected network of transcription factors. Among them, only Oct4 and Sox2 have been shown to be strictly required for the self-renewal of ESCs and pluripotency, particularly in culture conditions where differentiation cues are chemically inhibited. Here, we report that the conjunct activity of two orphan nuclear receptors, Esrrb and Nr5a2, parallels the importance of that of Oct4 and Sox2 in naïve ESCs. By occupying a large common set of regulatory elements, these two factors control the binding of Oct4, Sox2 and Nanog to DNA. Consequently, in their absence the pluripotency network collapses and the transcriptome is substantially deregulated, leading to the differentiation of ESCs. Altogether, this work identifies orphan nuclear receptors, previously thought to be performing supportive functions, as a new set of core regulators of naïve pluripotency.

Author(s):  
Nicola Festuccia ◽  
Nick Owens ◽  
Almira Chervova ◽  
Agnès Dubois ◽  
Pablo Navarro

The maintenance of pluripotency in mouse embryonic stem cells (ESCs) is governed by the action of an interconnected network of transcription factors. Among them, only Oct4 and Sox2 have been shown to be strictly required for the self-renewal of ESCs and pluripotency, particularly in culture conditions where differentiation cues are chemically inhibited. Here, we report that the conjunct activity of two orphan nuclear receptors, Esrrb and Nr5a2, parallels the importance of that of Oct4 and Sox2 in naïve ESCs. By occupying a large common set of regulatory elements, these two factors control the binding of Oct4, Sox2 and Nanog to DNA. Consequently, in their absence the pluripotency network collapses and the transcriptome is substantially deregulated, leading to the differentiation of ESCs. Altogether, this work identifies orphan nuclear receptors, previously thought to be performing supportive functions, as a new set of core regulators of naïve pluripotency.


PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34827 ◽  
Author(s):  
Erin L. Wuebben ◽  
Sunil K. Mallanna ◽  
Jesse L. Cox ◽  
Angie Rizzino

PLoS ONE ◽  
2016 ◽  
Vol 11 (3) ◽  
pp. e0150715 ◽  
Author(s):  
Hyojung Jeon ◽  
Tsuyoshi Waku ◽  
Takuya Azami ◽  
Le Tran Phuc Khoa ◽  
Jun Yanagisawa ◽  
...  

2011 ◽  
Vol 13 (6) ◽  
pp. 539-549 ◽  
Author(s):  
Ruchi Sharma ◽  
Aman George ◽  
Nitin Manchindra Kamble ◽  
Karn Pratap Singh ◽  
Manmohan Singh Chauhan ◽  
...  

2008 ◽  
Vol 411 (2) ◽  
pp. e5-e7 ◽  
Author(s):  
Angie Rizzino

Three transcription factors, Sox2, Oct-3/4 and Nanog, have been identified as master regulators that orchestrate mammalian embryogenesis as well as the self-renewal and pluripotency of ES (embryonic stem) cells. Efforts to understand how these transcription factors function have shown that they have a special property in common. Small changes in the expression of any one of these factors dramatically alter the self-renewal and pluripotency of ES cells. In this way, each functions as a molecular rheostat to control the behaviour of ES cells. Recent studies have begun to examine the molecular mechanisms that regulate the levels of these transcription factors. In this issue of the Biochemical Journal, Mullin and co-workers report that Nanog can self-associate to form dimers. Importantly, they also show that the domain responsible for dimerization is also needed for Nanog to sustain the self-renewal of ES cells in the absence of the cytokine LIF (leukaemia inhibitory factor). On the basis of their studies, they propose a novel mechanism for regulating the interactions between Nanog and other nuclear proteins.


2011 ◽  
Vol 112 (3) ◽  
pp. 942-948 ◽  
Author(s):  
Wei Wei Zhang ◽  
Xiao Jie Zhang ◽  
Hui Xian Liu ◽  
Jie Chen ◽  
Yong Hong Ren ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document