ArticleNature structural & molecular biology2024
Nucleosome-bound NR5A2 structure reveals pioneer factor mechanism by DNA minor groove anchor competition.
Article in Nature structural & molecular biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 21 citations in OpenAlex.
- Dose-resolved control of somatic reprogramming by Rora.Stem cell reports · 2026Article
- Feed-forward loops by NR5A2 ensure robust gene activation during pre-implantation development.Development (Cambridge, England) · 2026Article
- The Binding Landscape of an Essential Nuclear Hormone Receptor inbioRxiv : the preprint server for biology · 2025Article
- Genomic Crosstalk Between Nuclear Receptors in Hormone-dependent Cancers.Endocrinology · 2025Review
- DNA bendability regulates transcription factor binding to nucleosomes.Nature structural & molecular biology · 2025Article
- E2F1 induces a G0-G1 reentry transcriptional program without changing chromatin accessibility.bioRxiv : the preprint server for biology · 2025Article
- H2B.W2, a spermatocyte-specific histone variant, disrupts nucleosome stability, and reduces chromatin compaction.Nucleic acids research · 2025Article
- Structural basis of nucleosome binding and destabilization by the extended DNA binding domain of RFX5.Nucleic acids research · 2025Article
- Structural insights into the recognition of native nucleosomes by pioneer transcription factors.Current opinion in structural biology · 2025Review
- The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus.Nature reviews. Genetics · 2025Review
- Rise and SINE: roles of transcription factors and retrotransposons in zygotic genome activation.Nature reviews. Molecular cell biology · 2025Article
- Review
- Structural dynamics in chromatin unraveling by pioneer transcription factors.Biophysical reviews · 2024Review
- Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene expression during natural and induced reprogramming is controlled by pioneer transcription factors that initiate transcription from closed chromatin. Nr5a2 is a key pioneer factor that regulates zygotic genome activation in totipotent embryos, pluripotency in embryonic stem cells and metabolism in adult tissues, but the mechanism of its pioneer activity remains poorly understood. Here, we present a cryo-electron microscopy structure of human NR5A2 bound to a nucleosome. The structure shows that the conserved carboxy-terminal extension (CTE) loop of the NR5A2 DNA-binding domain competes with a DNA minor groove anchor of the nucleosome and releases entry-exit site DNA. Mutational analysis showed that NR5A2 D159 of the CTE is dispensable for DNA binding but required for stable nucleosome association and persistent DNA 'unwrapping'. These findings suggest that NR5A2 belongs to an emerging class of pioneer factors that can use DNA minor groove anchor competition to destabilize nucleosomes and facilitate gene expression during reprogramming.
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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.