ArticleMolecular cell2023
Chromatin regulation of transcriptional enhancers and cell fate by the Sotos syndrome gene NSD1.
Article in Molecular cell, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 41 citations in OpenAlex.
- Identifying critical lysines in mammalian histone H3 with high-throughput CRISPR prime editing.Nature genetics · 2026Article
- Single cell CRISPR screen identifies antagonism between Nsd1-H3K36me2 and Ezh2-H3K27me3 orchestrates pluripotency transition.Stem cell reports · 2026Article
- AURORA A interacts with DICER and SETD2 to promote S-phase progression.EMBO reports · 2026Article
- NSD1 governs H3K36me2-mediated DNA methylation and drives endo-mesodermal differentiation of human iPSCs.Clinical epigenetics · 2026Article
- SETD2 methyltransferase activity promotes correct transcription initiation and termination.EMBO reports · 2026Article
- Many faces of mammalian NSD methyltransferases.Cellular & molecular biology letters · 2026Review
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- Article
- Convergent DNA methylation abnormalities at enhancers and bivalent promoters in human growth disorders.Epigenetics & chromatin · 2025Article
- H3K36 Methylation as a Guardian of Epigenome Integrity.Nature communications · 2025Article
- Monitoring rapid degradation of NANOG reveals UTP15 maintains pluripotency by regulating nascent transcripts.Nature communications · 2025Article
- Reprogramming of H3K36me2 guides lineage-specific post-implantation de novo DNA methylation.Nature cell biology · 2025Article
- ELLA: modeling subcellular spatial variation of gene expression within cells in high-resolution spatial transcriptomics.Nature communications · 2025Article
- ZMYND11 Restrains KMT2A to Enable a Neuronal Developmental Program.bioRxiv : the preprint server for biology · 2025Article
- Congenital hypothyroidism in two children affected by Sotos syndrome: a simple association?Italian journal of pediatrics · 2025Article
- Paraspeckle protein NONO regulates active chromatin by allosterically stimulating NSD1.Cell reports · 2025Article
- Nuclear binding SET domain 1 alleviates cartilage ferroptosis in knee osteoarthritis by upregulating the krüppel-like factor 9/autophagy-related 14 pathway via H3K36me2 modification.Journal of cell communication and signaling · 2025Article
- The sotos syndrome gene Nsd1 safeguards developmental gene enhancers poised for transcription by maintaining the precise deposition of histone methylation.The Journal of biological chemistry · 2025Article
- Role and mechanisms of histone methylation in osteogenic/odontogenic differentiation of dental mesenchymal stem cells.International journal of oral science · 2025Review
- Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers.Nucleic acids research · 2025Article
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Authors and funding
10 authors at 2 institutions in 3 countries.
Funding
Abstract
Nuclear receptor-binding SET-domain protein 1 (NSD1), a methyltransferase that catalyzes H3K36me2, is essential for mammalian development and is frequently dysregulated in diseases, including Sotos syndrome. Despite the impacts of H3K36me2 on H3K27me3 and DNA methylation, the direct role of NSD1 in transcriptional regulation remains largely unknown. Here, we show that NSD1 and H3K36me2 are enriched at cis-regulatory elements, particularly enhancers. NSD1 enhancer association is conferred by a tandem quadruple PHD (qPHD)-PWWP module, which recognizes p300-catalyzed H3K18ac. By combining acute NSD1 depletion with time-resolved epigenomic and nascent transcriptomic analyses, we demonstrate that NSD1 promotes enhancer-dependent gene transcription by facilitating RNA polymerase II (RNA Pol II) pause release. Notably, NSD1 can act as a transcriptional coactivator independent of its catalytic activity. Moreover, NSD1 enables the activation of developmental transcriptional programs associated with Sotos syndrome pathophysiology and controls embryonic stem cell (ESC) multilineage differentiation. Collectively, we have identified NSD1 as an enhancer-acting transcriptional coactivator that contributes to cell fate transition and Sotos syndrome development.
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Registered trials
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.