ArticleProceedings of the National Academy of Sciences of the United States of America1999
Position-dependent inhibition of class-switch recombination by PGK-neor cassettes inserted into the immunoglobulin heavy chain constant region locus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 91 citations in OpenAlex.
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- Distinct plasmablast developmental intermediates produce graded expression of IgM secretory transcripts.Cell reports · 2025Article
- The role of chromatin loop extrusion in antibody diversification.Nature reviews. Immunology · 2022Review
- Physiological role of the 3'IgH CBEs super-anchor in antibody class switching.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Long-Range Control of Class Switch Recombination by Transcriptional Regulatory Elements.Frontiers in immunology · 2021Review
- Essential role of the initial activation signal in isotype selection upon deletion of a transcriptionally committed promoter.Scientific reports · 2019Article
- Article
- Two modes ofProceedings of the National Academy of Sciences of the United States of America · 2019Article
- Duplication of a germline promoter downstream of the IgH 3' regulatory region impairs class switch recombination.Scientific reports · 2018Article
- Dwarfism in homozygous Agc1Genesis (New York, N.Y. : 2000) · 2017Article
- Inducible CTCF insulator delays theProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Related Mechanisms of Antibody Somatic Hypermutation and Class Switch Recombination.Microbiology spectrum · 2015Review
- Polyclonal hyper-IgE mouse model reveals mechanistic insights into antibody class switch recombination.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Three-dimensional architecture of the IgH locus facilitates class switch recombination.Annals of the New York Academy of Sciences · 2012Article
- Enhancement of antibody class-switch recombination by the cumulative activity of four separate elements.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Enhanced expression of human cDNA by phosphoglycerate kinase promoter-puromycin cassette in the mouse transthyretin locus.Transgenic research · 2011Article
- The role of germline promoters and I exons in cytokine-induced gene-specific class switch recombination.Journal of immunology (Baltimore, Md. : 1950) · 2011Article
- Ectopic T cell receptor-α locus control region activity in B cells is suppressed by direct linkage to two flanking genes at once.PloS one · 2010Article
- Downstream class switching leads to IgE antibody production by B lymphocytes lacking IgM switch regions.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
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8 authors at 2 institutions in 1 country.
Funding
Abstract
The Ig heavy chain (IgH) constant region (CH) genes are organized from 5' to 3' in the order Cmicro, Cdelta, Cgamma3, Cgamma1, Cgamma2b, Cgamma2a, Cepsilon, and Calpha. Expression of CH genes downstream of Cdelta involves class-switch recombination (CSR), a process that is targeted by germ-line transcription (GT) of the corresponding CH gene. Previously, we demonstrated that insertion of a PGK-neor cassette at two sites downstream of Calpha inhibits, in cultured B cells, GT of and CSR to a subset of CH genes (including Cgamma3, Cgamma2a, Cgamma2b, and Cepsilon) that lie as far as 120 kb upstream. Here we show that insertion of the PGK-neor cassette in place of sequences in the Igamma2b locus inhibits GT of and CSR to the upstream Cgamma3 gene, but has no major effect on the downstream Cgamma2a and Cepsilon genes. Moreover, replacement of the Cepsilon exons with a PGK-neor cassette in the opposite transcriptional orientation also inhibits, in culture, GT of and CSR to the upstream Cgamma3, Cgamma2b, and Cgamma2a genes. As with the PGK-neor insertions 3' of Calpha studied previously, the Cgamma1 and Calpha genes were less affected by these mutations both in culture and in mice, whereas the Cgamma2b gene appeared less affected in vivo. Our findings support the existence of a long-range 3' IgH regulatory region required for GT of and CSR to multiple CH genes and suggest that PGK-neor cassette insertion into the locus short circuits the ability of this region to facilitate GT of dependent CH genes upstream of the insertion.
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