We need your help! If you've ever found our data helpful, please take our impact survey (15 min). Your replies will help keep the data flowing to the scientific community. Please Click here for Survey

Unknown

Dataset Information

0

Esrrb is a direct Nanog target gene that can substitute for Nanog function in pluripotent cells.


ABSTRACT: Embryonic stem cell (ESC) self-renewal efficiency is determined by the level of Nanog expression. However, the mechanisms by which Nanog functions remain unclear, and in particular, direct Nanog target genes are uncharacterized. Here we investigate ESCs expressing different Nanog levels and Nanog(-/-) cells with distinct functionally inducible Nanog proteins to identify Nanog-responsive genes. Surprisingly, these constitute a minor fraction of genes that Nanog binds. Prominent among Nanog-reponsive genes is Estrogen-related receptor b (Esrrb). Nanog binds directly to Esrrb, enhances binding of RNAPolII, and stimulates Esrrb transcription. Overexpression of Esrrb in ESCs maintains cytokine-independent self-renewal and pluripotency. Remarkably, this activity is retained in Nanog(-/-) ESCs. Moreover, Esrrb can reprogram Nanog(-/-) EpiSCs and can rescue stalled reprogramming in Nanog(-/-) pre-iPSCs. Finally, Esrrb deletion abolishes the defining ability of Nanog to confer LIF-independent ESC self-renewal. These findings are consistent with the functional placement of Esrrb downstream of Nanog.

SUBMITTER: Festuccia N 

PROVIDER: S-EPMC3473361 | BioStudies | 2012-01-01

REPOSITORIES: biostudies

Similar Datasets

2012-01-01 | S-EPMC3475801 | BioStudies
1000-01-01 | S-EPMC5775501 | BioStudies
1000-01-01 | S-EPMC5425684 | BioStudies
2015-01-01 | S-EPMC4535745 | BioStudies
2008-01-01 | S-EPMC2758041 | BioStudies
2015-01-01 | S-EPMC4409032 | BioStudies
2012-01-01 | S-EPMC3465555 | BioStudies
2014-01-01 | S-EPMC4227152 | BioStudies
2014-01-01 | S-EPMC3968261 | BioStudies
2019-01-01 | S-EPMC6376462 | BioStudies