NANOG assists in the establishment and maintenance of pluripotency by amplifying multiple signaling pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE107505 | GEO | 2018/11/29
REPOSITORIES: GEO
Similar Datasets
Project description:NANOG assists in the establishment and maintenance of pluripotency by amplifying multiple signaling pathways
| PRJNA420379 | ENA
Project description:Nanog affects establishment of chromatin marks at zebrafish Zygotic Genome Activation
| PRJNA600508 | ENA
Project description:Molecular control of the pluripotent state is thought to reside in a core circuitry of master transcription factors including the homeodomain-containing protein NANOG, which has an essential role in establishing ground state pluripotency during somatic cell reprogramming. Whereas the genomic occupancy of NANOG has been extensively investigated, comparatively little is known about NANOG-associated proteins and their contribution to the NANOG-mediated reprogramming process. Using enhanced purification techniques and a stringent computational algorithm, we identify 27 high-confidence protein interaction partners of NANOG in mouse embryonic stem cells. These consist of 19 previously unknown partners of NANOG that have not been reported before, including the ten-eleven translocation (TET) family methylcytosine hydroxylase TET1. We confirm physical association of NANOG with TET1, and demonstrate that TET1, in synergy with NANOG, enhances the efficiency of reprogramming. We also find physical association and reprogramming synergy of TET2 with NANOG, and demonstrate that knockdown of TET2 abolishes the reprogramming synergy of NANOG with a catalytically deficient mutant of TET1. These results indicate that the physical interaction between NANOG and TET1/TET2 proteins facilitates reprogramming in a manner that is dependent on the catalytic activity of TET1/TET2. TET1 and NANOG co-occupy genomic loci of genes associated with both maintenance of pluripotency and lineage commitment in embryonic stem cells, and TET1 binding is reduced upon NANOG depletion. Co-expression of NANOG and TET1 increases 5-hydroxymethylcytosine levels at the top-ranked common target loci Esrrb and Oct4 (also called Pou5f1), resulting in priming of their expression before reprogramming to naive pluripotency. We propose that TET1 is recruited by NANOG to enhance the expression of a subset of key reprogramming target genes. These results provide an insight into the reprogramming mechanism of NANOG and uncover a new role for 5-methylcytosine hydroxylases in the establishment of naive pluripotency.
| S-EPMC3606645 | biostudies-literature
Project description:The COP9 signalosome has been implicated in pluripotency maintenance of human embryonic stem cells. Yet, the mechanism for the COP9 signalosome to regulate pluripotency remains elusive. Through knocking down individual COP9 subunits, we demonstrate that Cops2, but not the whole COP9 signalosome, is essential for pluripotency maintenance in mouse embryonic stem cells. Down-regulation of Cops2 leads to reduced expression of pluripotency genes, slower proliferation rate, G2/M cell cycle arrest, and compromised embryoid differentiation of embryonic stem cells. Cops2 also facilitates somatic cell reprogramming. We further show that Cops2 binds to Nanog protein and prevent the degradation of Nanog by proteasome. Moreover, Cops2 functions as transcriptional corepressor to facilitate pluripotency maintenance. Altogether, our data reveal the essential role and novel mechanisms of Cops2 in pluripotency maintenance.
| S-EPMC4881025 | biostudies-literature
Project description:In zebrafish embryos, the maternal transcription factors (TFs)Nanog, Pou5f3 and Sox19b activate the early zygotic gene expression. To evaluate the role of Nanog, we examined the changes in H3K27ac and H3K4me3 chromatin modifications in the MZnanog embryos mutant by maternal and zygotic Nanog.
2020-05-07 | GSE143439 | GEO
Project description:NANOG is required for the long-term establishment of avian somatic reprogrammed cells
| PRJNA432454 | ENA
Project description:Pluripotency is regulated by a network of transcription factors that maintains early embryonic cells in an undifferentiated state while allowing them to proliferate. NANOG is a critical factor for maintaining pluripotency and its role in primordial germ cell differentiation has been well described. However, Nanog is expressed during gastrulation across all the posterior epiblast, and only later in development its expression is restricted to primordial germ cells. In this work, we unveiled a previously unknown mechanism by which Nanog specifically represses genes involved in anterior epiblast lineage. Analysis of transcriptional data from both embryonic stem cells and gastrulating mouse embryos revealed Pou3f1 expression to be negatively correlated with that of Nanog during the early stages of differentiation. We have functionally demonstrated Pou3f1 to be a direct target of NANOG by using a dual transgene system for the controlled expression of Nanog. Use of Nanog null ES cells further demonstrated a role for Nanog in repressing a subset of anterior neural genes. Deletion of a NANOG binding site (BS) located nine kilobases downstream of the transcription start site of Pou3f1 revealed this BS to have a specific role in the regionalization of the expression of this gene in the embryo. Our results indicate an active role of Nanog inhibiting neural regulatory networks by repressing Pou3f1 at the onset of gastrulation.
2019-10-31 | GSE138818 | GEO
Project description:NANOG is a key transcription factor for pluripotency in embryonic stem cells. However, its role in adult tissues remains largely unexplored. Here, we show that mouse NANOG is expressed in the progenitor layer of stratified epithelia, including esophagus, forestomach and skin. Accordingly, the Nanog promoter is hypomethylated in the epithelial layers of the esophagus and forestomach. Interestingly, ubiquitous transgenic overexpression of NANOG in mice induces hyperplasia in stratified epithelia, but not in other tissues. Mechanistically, we show that NANOG transcriptionally activates the mitotic program selectively in stratified epithelia, and endogenous NANOG directly binds the Aurora kinase A (Aurka) promoter in keratinocytes. Finally, human and mouse squamous cell carcinomas (SCCs) express NANOG and its levels positively correlate with those of AURKA in human head and neck SCCs. Together, these results implicate a lineage-restricted mitogenic role of NANOG in normal stratified epithelia and its derived carcinomas.
2014-06-27 | GSE48370 | GEO
Project description:Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.
2017-02-21 | GSE91021 | GEO
Project description:Despite the requirement of Sin3a for survival of early embryos and embryonic stem cells (ESCs), mechanistic action of Sin3a in the maintenance and establishment of pluripotency remains unexplored. Here we report the transcriptional regulatory roles of Sin3a in maintaining ESC pluripotency and in reprogramming somatic cells towards full pluripotency. Sin3a/HDAC complex members were enriched in an extended Nanog interactome and exhibited a predominant transcriptional co-activator role at a global level in ESCs. We also established a critical role for Sin3a in efficient reprogramming of somatic cells towards full pluripotency. Nanog and Sin3a co-localize at almost all of their genome-wide targets in pre-iPSCs, and both factors are required to directly induce a synergistic transcriptional program wherein pluripotency genes are activated and reprogramming barrier genes are repressed. Our results, for the first time, establish positive roles of the Sin3a/HDAC complex in the maintenance and establishment of pluripotency.
2017-02-21 | GSE90986 | GEO