ArticleNature immunology2009
HoxC4 binds to the promoter of the cytidine deaminase AID gene to induce AID expression, class-switch DNA recombination and somatic hypermutation.
Article in Nature immunology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It carries an expression of concern. Cited by 91 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
91 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
- Identification of multiple risk loci and regulatory mechanisms influencing susceptibility to multiple myeloma.Nature communications · 2018Pooled it
- Toll-like receptor signaling pathway in chronic lymphocytic leukemia: distinct gene expression profiles of potential pathogenic significance in specific subsets of patients.Haematologica · 2011Trial
- B cell TET2 recruits OGT for nuclear TET2 and H2B O-GlcNAcylation to drive AID and BLIMP-1 expression and maturation of the antibody response.Cell reports · 2026Article
- Unlocking the HOX: Homeobox Genes as Regulators of Hematopoietic Development.International journal of molecular sciences · 2026Review
- Understanding the effect of estrogen on B cells: implications for immune health and autoimmunity.American journal of physiology. Cell physiology · 2026Review
- Imbalanced IgA-IgG class switching recombination: a novel mechanism of gut immune dysregulation in inflammatory bowel disease.Frontiers in immunology · 2026Review
- FoxO1 signaling in B cell malignancies and its therapeutic targeting.FEBS letters · 2025Review
- A humanized mouse that mounts mature class-switched, hypermutated and neutralizing antibody responses.Nature immunology · 2024Article
- CD62L expression marks a functionally distinct subset of memory B cells.Cell reports · 2023Article
- Mechanism and regulation of secondary immunoglobulin diversification.Cell cycle (Georgetown, Tex.) · 2023Review
- A Noise-Tolerating Gene Association Network Uncovering an Oncogenic Regulatory Motif in Lymphoma Transcriptomics.Life (Basel, Switzerland) · 2023Article
- Sex chromosome complement and sex steroid signaling underlie sex differences in immunity to respiratory virus infection.Frontiers in pharmacology · 2023Review
- Rad52 mediates class-switch DNA recombination to IgD.Nature communications · 2022Article
- B cell class switching in intestinal immunity in health and disease.Scandinavian journal of immunology · 2022Review
- USP10 regulates B cell response to SARS-CoV-2 or HIV-1 nanoparticle vaccines through deubiquitinating AID.Signal transduction and targeted therapy · 2022Article
- Sex bias in lymphocytes: Implications for autoimmune diseases.Frontiers in immunology · 2022Review
- OCT2 pre-positioning facilitates cell fate transition and chromatin architecture changes in humoral immunity.Nature immunology · 2021Article
- Transcriptomes of an Array of Chicken Ovary, Intestinal, and Immune Cells and Tissues.Frontiers in genetics · 2021Article
- AID in Chronic Lymphocytic Leukemia: Induction and Action During Disease Progression.Frontiers in oncology · 2021Review
- Epigenetic Modulation of Class-Switch DNA Recombination to IgA by miR-146a Through Downregulation of Smad2, Smad3 and Smad4.Frontiers in immunology · 2021Article
31 more citing papers are in PubMed but not listed here.
Corrections and comments
- Expression of concern
Authors and funding
9 authors at 1 institution in 1 country.
Funding
Abstract
The cytidine deaminase AID (encoded by Aicda in mice and AICDA in humans) is critical for immunoglobulin class-switch recombination (CSR) and somatic hypermutation (SHM). Here we show that AID expression was induced by the HoxC4 homeodomain transcription factor, which bound to a highly conserved HoxC4-Oct site in the Aicda or AICDA promoter. This site functioned in synergy with a conserved binding site for the transcription factors Sp1, Sp3 and NF-kappaB. HoxC4 was 'preferentially' expressed in germinal center B cells and was upregulated by engagement of CD40 by CD154, as well as by lipopolysaccharide and interleukin 4. HoxC4 deficiency resulted in impaired CSR and SHM because of lower AID expression and not some other putative HoxC4-dependent activity. Enforced expression of AID in Hoxc4(-/-) B cells fully restored CSR. Thus, HoxC4 directly activates the Aicda promoter, thereby inducing AID expression, CSR and SHM.
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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.