ArticleStem cells (Dayton, Ohio)2011
Differential recruitment of methyl CpG-binding domain factors and DNA methyltransferases by the orphan receptor germ cell nuclear factor initiates the repression and silencing of Oct4.
Article in Stem cells (Dayton, Ohio), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
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- Breast cancer cell resistance to hormonal and targeted therapeutics is correlated with the inactivation of the NR6A1 axis.Cancer drug resistance (Alhambra, Calif.) · 2024Article
- The expanding roles of Nr6a1 in development and evolution.Frontiers in cell and developmental biology · 2024Review
- Nr6a1 controls Hox expression dynamics and is a master regulator of vertebrate trunk development.Nature communications · 2022Article
- microRNA-196a-5p inhibits testicular germ cell tumor progression via NR6A1/E-cadherin axis.Cancer medicine · 2020Article
- A Novel 13 bp Deletion within theAnimals : an open access journal from MDPI · 2019Article
- ERα is required for suppressing OCT4-induced proliferation of breast cancer cells via DNMT1/ISL1/ERK axis.Cell proliferation · 2019Article
- Imprinted gene Zinc finger protein 127 is a novel regulator of master pluripotency transcription factor, Oct4.BMB reports · 2018Article
- Oct4 regulates DNA methyltransferase 1 transcription by direct binding of the regulatory element.Cellular & molecular biology letters · 2018Article
- Specific or not specific recruitment of DNMTs for DNA methylation, an epigenetic dilemma.Clinical epigenetics · 2018Review
- Nuclear receptors in neural stem/progenitor cell homeostasis.Cellular and molecular life sciences : CMLS · 2017Review
- A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).Journal of molecular biology · 2016Article
- Emerging Molecular and Biological Functions of MBD2, a Reader of DNA Methylation.Frontiers in genetics · 2016Review
- Genome-editing tools for stem cell biology.Cell death & disease · 2015Review
- RAR/RXR binding dynamics distinguish pluripotency from differentiation associated cis-regulatory elements.Nucleic acids research · 2015Article
- Transcriptional regulatory events initiated by Ascl1 and Neurog2 during neuronal differentiation of P19 embryonic carcinoma cells.Journal of molecular neuroscience : MN · 2015Article
- GCNF-dependent activation of cyclin D1 expression via repression of Mir302a during ESC differentiation.Stem cells (Dayton, Ohio) · 2014Article
- Article
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Authors and funding
5 authors at 2 institutions in 3 countries.
Funding
Abstract
The pluripotency gene Oct4 encodes a key transcription factor that maintains self-renewal of embryonic stem cell (ESC) and is downregulated upon differentiation of ESCs and silenced in somatic cells. A combination of cis elements, transcription factors, and epigenetic modifications, such as DNA methylation, mediates Oct4 gene expression. Here, we show that the orphan nuclear receptor germ cell nuclear factor (GCNF) initiates Oct4 repression and DNA methylation by the differential recruitment of methyl-CpG binding domain (MBD) and DNA methyltransferases (Dnmts) to the Oct4 promoter. When compared with wild-type ESCs and gastrulating embryos, Oct4 repression is lost and its proximal promoter is significantly hypomethylated in retinoic acid (RA)-differentiated GCNF(-/-) ESCs and GCNF(-/-) embryos. Efforts to characterize mediators of GCNF's repressive function and DNA methylation of the Oct4 promoter identified MBD3, MBD2, and de novo Dnmts as GCNF interacting factors. Upon differentiation, endogenous GCNF binds to the Oct4 proximal promoter and differentially recruits MBD3 and MBD2 as well as Dnmt3A. In differentiated GCNF(-/-) ESCs, recruitment of MBD3 and MBD2 as well as Dnmt3A to Oct4 promoter is lost and subsequently Oct4 repression and DNA methylation failed to occur. Hypomethylation of the Oct4 promoter is also observed in RA-differentiated MBD3(-/-) and Dnmt3A(-/-) ESCs, but not in MBD2(-/-) and Dnmt3B(-/-) ESCs. Thus, recruitment of MBD3, MBD2, and Dnmt3A by GCNF links two events: gene-specific repression and DNA methylation, which occur differentially at the Oct4 promoter. GCNF initiates the repression and epigenetic modification of Oct4 gene during ESC differentiation.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.