ArticlePLoS genetics2012
The DSIF subunits Spt4 and Spt5 have distinct roles at various phases of immunoglobulin class switch recombination.
Article in PLoS genetics, 2012. 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, 46 citations in OpenAlex.
- BRIP1, a G-quadruplex DNA helicase, protects against AID-induced genomic instability by limiting R-loop accumulation.Molecular medicine (Cambridge, Mass.) · 2026Article
- hnRNPL-CstF64 complex: coordinating CSR and LSR in IgH locus recombination dynamics through eRNA and NHEJ regulation.Nucleic acids research · 2025Article
- BRD2 promotes antibody class switch recombination by facilitating DNA repair in collaboration with NIPBL.Nucleic acids research · 2024Article
- Lowering mutant huntingtin by small molecules relieves Huntington's disease symptoms and progression.EMBO molecular medicine · 2024Article
- Article
- Senataxin and RNase H2 act redundantly to suppress genome instability during class switch recombination.eLife · 2022Article
- AFF3, a susceptibility factor for autoimmune diseases, is a molecular facilitator of immunoglobulin class switch recombination.Science advances · 2022Article
- Promoter Proximity Defines Mutation Window for VJournal 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
- SPT6-driven error-free DNA repair safeguards genomic stability of glioblastoma cancer stem-like cells.Nature communications · 2020Article
- Polo kinase recruitment via the constitutive centromere-associated network at the kinetochore elevates centromeric RNA.PLoS genetics · 2020Article
- Uncoupling Splicing From Transcription Using Antisense Oligonucleotides Reveals a Dual Role for I Exon Donor Splice Sites in Antibody Class Switching.Frontiers in immunology · 2020Article
- Regulation of RNA polymerase II processivity by Spt5 is restricted to a narrow window during elongation.The EMBO journal · 2018Article
- Epigenomic Modifications Mediating Antibody Maturation.Frontiers in immunology · 2018Review
- Spt5 Plays Vital Roles in the Control of Sense and Antisense Transcription Elongation.Molecular cell · 2017Article
- The elongation factor Spt5 facilitates transcription initiation for rapid induction of inflammatory-response genes.Nature communications · 2016Article
- Analysis of Subcellular RNA Fractions Revealed a Transcription-Independent Effect of Tumor Necrosis Factor Alpha on Splicing, Mediated by Spt5.Molecular and cellular biology · 2016Article
- Chromatin remodeller SMARCA4 recruits topoisomerase 1 and suppresses transcription-associated genomic instability.Nature communications · 2016Article
- Suppressor of Ty homolog-5, a novel tumor-specific human telomerase reverse transcriptase promoter-binding protein and activator in colon cancer cells.Oncotarget · 2015Article
- Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Class-switch recombination (CSR), induced by activation-induced cytidine deaminase (AID), can be divided into two phases: DNA cleavage of the switch (S) regions and the joining of the cleaved ends of the different S regions. Here, we show that the DSIF complex (Spt4 and Spt5), a transcription elongation factor, is required for CSR in a switch-proficient B cell line CH12F3-2A cells, and Spt4 and Spt5 carry out independent functions in CSR. While neither Spt4 nor Spt5 is required for transcription of S regions and AID, expression array analysis suggests that Spt4 and Spt5 regulate a distinct subset of transcripts in CH12F3-2A cells. Curiously, Spt4 is critically important in suppressing cryptic transcription initiating from the intronic Sμ region. Depletion of Spt5 reduced the H3K4me3 level and DNA cleavage at the Sα region, whereas Spt4 knockdown did not perturb the H3K4me3 status and S region cleavage. H3K4me3 modification level thus correlated well with the DNA breakage efficiency. Therefore we conclude that Spt5 plays a role similar to the histone chaperone FACT complex that regulates H3K4me3 modification and DNA cleavage in CSR. Since Spt4 is not involved in the DNA cleavage step, we suspected that Spt4 might be required for DNA repair in CSR. We examined whether Spt4 or Spt5 is essential in non-homologous end joining (NHEJ) and homologous recombination (HR) as CSR utilizes general repair pathways. Both Spt4 and Spt5 are required for NHEJ and HR as determined by assay systems using synthetic repair substrates that are actively transcribed even in the absence of Spt4 and Spt5. Taken together, Spt4 and Spt5 can function independently in multiple transcription-coupled steps of CSR.
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