ArticleThe Journal of biological chemistry2012
The histone chaperone Spt6 is required for activation-induced cytidine deaminase target determination through H3K4me3 regulation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 80 citations in OpenAlex.
- Article
- Genetic alterations in SUPT6H are associated with neurodevelopmental disorders.Biochimica et biophysica acta. Molecular basis of disease · 2026Article
- R-loop disruption triggers irreversible topoisomerase 1-DNA cleavage complex formation during AID-dependent IgH gene diversification.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Epigenetic dysregulation of B‑cells in autoimmune diseases and lymphomas (Review).International journal of molecular medicine · 2026Review
- Somatic hypermutation patterns are shaped by both motif position and sequence grammar.The EMBO journal · 2026Article
- Long non‑coding RNA ABHD11‑AS1 inhibits colorectal cancer progression through interacting with EGFR to suppress the EGFR/ERK signaling pathway.International journal of oncology · 2025Article
- Conserved role of hnRNPL in alternative splicing of epigenetic modifiers enables B cell activation.EMBO reports · 2024Article
- Interpretable deep learning reveals the role of an E-box motif in suppressing somatic hypermutation of AGCT motifs within human immunoglobulin variable regions.Frontiers in immunology · 2024Article
- Insights into Spt6: a histone chaperone that functions in transcription, DNA replication, and genome stability.Trends in genetics : TIG · 2023Review
- The conserved histone chaperone Spt6 is strongly required for DNA replication and genome stability.Cell reports · 2023Article
- XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation.Science advances · 2022Article
- AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination.Science advances · 2022Article
- Activation induced cytidine deaminase: An old friend with new faces.Frontiers in immunology · 2022Review
- Recognition of driver genes with potential prognostic implications in lung adenocarcinoma based on H3K79me2.Computational and structural biotechnology journal · 2022Article
- Ig Enhancers Increase RNA Polymerase II Stalling at Somatic Hypermutation Target Sequences.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Phf5a regulates DNA repair in class switch recombination via p400 and histone H2A variant deposition.The EMBO journal · 2021Article
- Chemotherapy-induced S100A10 recruits KDM6A to facilitate OCT4-mediated breast cancer stemness.The Journal of clinical investigation · 2020Article
- SAMHD1-mediated dNTP degradation is required for efficient DNA repair during antibody class switch recombination.The EMBO journal · 2020Article
- AID in Antibody Diversification: There and Back Again.Trends in immunology · 2020Review
- Regulatory mechanisms of B cell responses and the implication in B cell-related diseases.Journal of biomedical science · 2019Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
H3K4me3 plays a critical role in the activation-induced cytidine deaminase (AID)-induced DNA cleavage of switch (S) regions in the immunoglobulin heavy chain (IgH) locus during class-switch recombination (CSR). The histone chaperone complex facilitates chromatin transcription (FACT) is responsible for forming H3K4me3 at AID target loci. Here we show that the histone chaperone suppressor of Ty6 (Spt6) also participates in regulating H3K4me3 for CSR and for somatic hypermutation in AID target loci. We found that H3K4me3 loss was correlated with defects in AID-induced DNA breakage and reduced mutation frequencies in IgH loci in both S and variable regions and in non-IgH loci such as metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and small nucleolar RNA host gene 3 (SNHG3). Global gene expression analysis revealed that Spt6 can act as both a positive and negative transcriptional regulator in B cells, affecting ∼5% of the genes that includes suppressor of Ty4 (Spt4) and AID. Interestingly, Spt6 regulates CSR and AID expression through two distinct histone modification pathways, H3K4me3 and H3K36me3, respectively. Tandem SH2 domain of Spt6 plays a critical role in CSR and H3K4me3 regulation involving Set1 histone methyltransferase. We conclude that Spt6 is a unique histone chaperone capable of regulating the histone epigenetic state of both AID targets and the AID locus.
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