ArticleScience advances2021
The SAM domain-containing protein 1 (SAMD1) acts as a repressive chromatin regulator at unmethylated CpG islands.
Article in Science advances, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 37 citations in OpenAlex.
- More than SAM: mechanisms of action of the Polycomb group protein polyhomeotic.Nucleus (Austin, Tex.) · 2026Review
- Article
- Novel intermolecular zinc fingers and redox-driven conformational changes dictate tumor suppressor ZMYND11's role in cooperative recognition of diverse targets.Nucleic acids research · 2026Article
- The SAMD1 transcription factor coordinates hematopoietic lineage differentiation and H3K4 methylation status.Blood advances · 2025Article
- Targeting Prostate Cancer Metabolism Through Transcriptional and Epigenetic Modulation: A Multi-Target Approach to Therapeutic Innovation.International journal of molecular sciences · 2025Review
- Cooperation of a polymerizing SAM domain and an intrinsically disordered region enables full SAMD1 function on chromatin.Nucleic acids research · 2025Article
- The transcribed ultraconserved regions: emerging players in colorectal cancer biology and therapy.Frontiers in cell and developmental biology · 2025Review
- Oncoprotein LAMTOR5-mediated CHOP silence via DNA hypermethylation and miR-182/miR-769 in promotion of liver cancer growth.Acta pharmacologica Sinica · 2024Article
- Structural basis of DNA recognition by BEN domain proteins reveals a role for oligomerization in unmethylated DNA selection by BANP.Nucleic acids research · 2024Article
- SAMD1 suppresses epithelial-mesenchymal transition pathways in pancreatic ductal adenocarcinoma.PLoS biology · 2024Article
- Structural analysis of the SAM domain of the Arabidopsis mitochondrial tRNA import receptor.The Journal of biological chemistry · 2024Article
- Characterization of winged helix domain fusion endonucleases as N6-methyladenine-dependent type IV restriction systems.Frontiers in microbiology · 2024Article
- SAMD1 attenuates antiphospholipid syndrome-induced pregnancy complications.Immunity, inflammation and disease · 2023Article
- Sticky, Adaptable, and Many-sided: SAM protein versatility in normal and pathological hematopoietic states.BioEssays : news and reviews in molecular, cellular and developmental biology · 2023Review
- H3K4me3-related lncRNAs signature and comprehensive analysis of H3K4me3 regulating tumor immunity in lung adenocarcinoma.Respiratory research · 2023Article
- Investigation of SAMD1 ablation in mice.Scientific reports · 2023Article
- The histone acetyltransferase KAT6A is recruited to unmethylated CpG islands via a DNA binding winged helix domain.Nucleic acids research · 2023Article
- Article
- Generating specificity in genome regulation through transcription factor sensitivity to chromatin.Nature reviews. Genetics · 2022Review
- SAMD1 attenuates antiphospholipid syndrome-induced vascular injury and pregnancy complications.Immunity, inflammation and disease · 2022Article
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
CpG islands (CGIs) are key regulatory DNA elements at most promoters, but how they influence the chromatin status and transcription remains elusive. Here, we identify and characterize SAMD1 (SAM domain-containing protein 1) as an unmethylated CGI-binding protein. SAMD1 has an atypical winged-helix domain that directly recognizes unmethylated CpG-containing DNA via simultaneous interactions with both the major and the minor groove. The SAM domain interacts with L3MBTL3, but it can also homopolymerize into a closed pentameric ring. At a genome-wide level, SAMD1 localizes to H3K4me3-decorated CGIs, where it acts as a repressor. SAMD1 tethers L3MBTL3 to chromatin and interacts with the KDM1A histone demethylase complex to modulate H3K4me2 and H3K4me3 levels at CGIs, thereby providing a mechanism for SAMD1-mediated transcriptional repression. The absence of SAMD1 impairs ES cell differentiation processes, leading to misregulation of key biological pathways. Together, our work establishes SAMD1 as a newly identified chromatin regulator acting at unmethylated CGIs.
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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.