ArticleThe Journal of experimental medicine2016
Mediator facilitates transcriptional activation and dynamic long-range contacts at the IgH locus during class switch recombination.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- Core enhancers of the 3'RR optimize IgH nuclear position and loop conformation for successful oriented class switch recombination.Nucleic acids research · 2024Article
- How Estrogen, Testosterone, and Sex Differences Influence Serum Immunoglobulin Isotype Patterns in Mice and Humans.Viruses · 2023Article
- XLID syndrome gene Med12 promotes Ig isotype switching through chromatin modification and enhancer RNA regulation.Science advances · 2022Article
- Microbiome Shapes the T Cell Receptor Repertoire among CD4+CD8+ Thymocytes.Biomedicines · 2022Article
- The Mediator kinase module: an interface between cell signaling and transcription.Trends in biochemical sciences · 2022Review
- Long-Range Control of Class Switch Recombination by Transcriptional Regulatory Elements.Frontiers in immunology · 2021Review
- Unique Immune Cell Coactivators Specify Locus Control Region Function and Cell Stage.Molecular cell · 2020Article
- Epigenomics-based identification of oestrogen-regulated long noncoding RNAs in ER+ breast cancer.RNA biology · 2020Article
- Three-dimensional genome rewiring during the development of antibody-secreting cells.Biochemical Society transactions · 2020Review
- Spt5-mediated enhancer transcription directly couples enhancer activation with physical promoter interaction.Nature genetics · 2020Article
- From Influenza Virus Infections to Lupus: Synchronous Estrogen ReceptorViral immunology · 2020Article
- CDK-Mediator and FBXL19 prime developmental genes for activation by promoting atypical regulatory interactions.Nucleic acids research · 2020Article
- Matters of life and death: How estrogen and estrogen receptor binding to the immunoglobulin heavy chain locus may influence outcomes of infection, allergy, and autoimmune disease.Cellular immunology · 2019Review
- A novel regulatory region controls IgH locus transcription and switch recombination to a subset of isotypes.Cellular & molecular immunology · 2019Article
- Two modes ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Role of chromosomal architecture in germinal center B cells and lymphomagenesis.Current opinion in hematology · 2019Review
- Aberrant activation of CYR61 enhancers in colorectal cancer development.Journal of experimental & clinical cancer research : CR · 2019Article
- Complex sex-biased antibody responses: estrogen receptors bind estrogen response elements centered within immunoglobulin heavy chain gene enhancers.International immunology · 2019Article
- Developmental regulation of DNA cytosine methylation at the immunoglobulin heavy chain constant locus.PLoS genetics · 2019Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 3 countries.
Funding
Abstract
Immunoglobulin (Ig) class switch recombination (CSR) is initiated by the transcription-coupled recruitment of activation-induced cytidine deaminase (AID) to Ig switch regions (S regions). During CSR, the IgH locus undergoes dynamic three-dimensional structural changes in which promoters, enhancers, and S regions are brought to close proximity. Nevertheless, little is known about the underlying mechanisms. In this study, we show that Med1 and Med12, two subunits of the mediator complex implicated in transcription initiation and long-range enhancer/promoter loop formation, are dynamically recruited to the IgH locus enhancers and the acceptor regions during CSR and that their knockdown in CH12 cells results in impaired CSR. Furthermore, we show that conditional inactivation of Med1 in B cells results in defective CSR and reduced acceptor S region transcription. Finally, we show that in B cells undergoing CSR, the dynamic long-range contacts between the IgH enhancers and the acceptor regions correlate with Med1 and Med12 binding and that they happen at a reduced frequency in Med1-deficient B cells. Our results implicate the mediator complex in the mechanism of CSR and are consistent with a model in which mediator facilitates the long-range contacts between S regions and the IgH locus enhancers during CSR and their transcriptional activation.
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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.