ArticleNucleic acids research2023
The homeodomain of Oct4 is a dimeric binder of methylated CpG elements.
Article in Nucleic acids research, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Identification of methylation-sensitive human transcription factors using meSMiLE-seq.Nature communications · 2026Article
- Methylation profile characteristics in the H19/IGF2:IG-DMR revealed by long-read sequencing analysis in patients with Beckwith-Wiedemann syndrome having defects in the OCT4/SOX2 binding site.Clinical epigenetics · 2026Article
- Control of Gene Expression by Proteins That Bind Many Alternative Nucleic Acid Structures Through the Same Domain.International journal of molecular sciences · 2025Article
- Jade1 and the HBO1 histone acetyltransferase complex are spatial-selective cofactors of the pluripotency transcription factor Oct4.The Journal of biological chemistry · 2025Article
- Coupled Heterogeneity to Dimeric Site-Specific Binding by the POU-Family Transcription Factor OCT2.The journal of physical chemistry. B · 2025Article
- The emergence of Sox and POU transcription factors predates the origins of animal stem cells.Nature communications · 2024Article
- DNA-binding proteins from MBD through ZF to BEN: recognition of cytosine methylation status by one arginine with two conformations.Nucleic acids research · 2024Article
- Epigenomic insights into common human disease pathology.Cellular and molecular life sciences : CMLS · 2024Review
- Pioneer factors: roles and their regulation in development.Trends in genetics : TIG · 2024Review
- Transcriptional Coactivator BOB1 (OBF1, OCA-B) Modulates the Specificity of DNA Recognition by the POU-Domain Factors OCT1 and OCT2 in a Monomeric Configuration.Biomolecules · 2024Article
- Evaluation of the determinants for improved pluripotency induction and maintenance by engineered SOX17.Nucleic acids research · 2023Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 5 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Oct4 is essential to maintain pluripotency and has a pivotal role in establishing the germline. Its DNA-binding POU domain was recently found to bind motifs with methylated CpG elements normally associated with epigenetic silencing. However, the mode of binding and the consequences of this capability has remained unclear. Here, we show that Oct4 binds to a compact palindromic DNA element with a methylated CpG core (CpGpal) in alternative states of pluripotency and during cellular reprogramming towards induced pluripotent stem cells (iPSCs). During cellular reprogramming, typical Oct4 bound enhancers are uniformly demethylated, with the prominent exception of the CpGpal sites where DNA methylation is often maintained. We demonstrate that Oct4 cooperatively binds the CpGpal element as a homodimer, which contrasts with the ectoderm-expressed POU factor Brn2. Indeed, binding to CpGpal is Oct4-specific as other POU factors expressed in somatic cells avoid this element. Binding assays combined with structural analyses and molecular dynamic simulations show that dimeric Oct4-binding to CpGpal is driven by the POU-homeodomain whilst the POU-specific domain is detached from DNA. Collectively, we report that Oct4 exerts parts of its regulatory function in the context of methylated DNA through a DNA recognition mechanism that solely relies on its homeodomain.
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