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S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination
Immunoglobulin class switch recombination is governed by long-range interactions between enhancers and germline transcript promoters to activate transcription and modulate chromatin accessibility to activation-induced cytidine deaminase (AID). However, mechanisms leading to the differential targetin...
Autores principales: | , , , , |
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Formato: | Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722165/ https://www.ncbi.nlm.nih.gov/pubmed/19596805 http://dx.doi.org/10.1084/jem.20081678 |
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author | Wang, Lili Wuerffel, Robert Feldman, Scott Khamlichi, Ahmed Amine Kenter, Amy L. |
author_facet | Wang, Lili Wuerffel, Robert Feldman, Scott Khamlichi, Ahmed Amine Kenter, Amy L. |
author_sort | Wang, Lili |
collection | PubMed |
description | Immunoglobulin class switch recombination is governed by long-range interactions between enhancers and germline transcript promoters to activate transcription and modulate chromatin accessibility to activation-induced cytidine deaminase (AID). However, mechanisms leading to the differential targeting of AID to switch (S) regions but not to constant (C(H)) regions remain unclear. We show that S and C(H) regions are dynamically modified with histone marks that are associated with active and repressed chromatin states, respectively. Chromatin accessibility is superimposable with the activating histone modifications, which extend throughout S regions irrespective of length. High density elongating RNA polymerase II (RNAP II) is detected in S regions, suggesting that the transcription machinery has paused and stalling is abolished by deletion of the S region. We propose that RNAP II enrichment facilitates recruitment of histone modifiers to generate accessibility. Thus, the histone methylation pattern produced by transcription localizes accessible chromatin to S regions, thereby focusing AID attack. |
format | Text |
id | pubmed-2722165 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-27221652010-02-03 S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination Wang, Lili Wuerffel, Robert Feldman, Scott Khamlichi, Ahmed Amine Kenter, Amy L. J Exp Med Article Immunoglobulin class switch recombination is governed by long-range interactions between enhancers and germline transcript promoters to activate transcription and modulate chromatin accessibility to activation-induced cytidine deaminase (AID). However, mechanisms leading to the differential targeting of AID to switch (S) regions but not to constant (C(H)) regions remain unclear. We show that S and C(H) regions are dynamically modified with histone marks that are associated with active and repressed chromatin states, respectively. Chromatin accessibility is superimposable with the activating histone modifications, which extend throughout S regions irrespective of length. High density elongating RNA polymerase II (RNAP II) is detected in S regions, suggesting that the transcription machinery has paused and stalling is abolished by deletion of the S region. We propose that RNAP II enrichment facilitates recruitment of histone modifiers to generate accessibility. Thus, the histone methylation pattern produced by transcription localizes accessible chromatin to S regions, thereby focusing AID attack. The Rockefeller University Press 2009-08-03 /pmc/articles/PMC2722165/ /pubmed/19596805 http://dx.doi.org/10.1084/jem.20081678 Text en © 2009 Wang et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.jem.org/misc/terms.shtml). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Article Wang, Lili Wuerffel, Robert Feldman, Scott Khamlichi, Ahmed Amine Kenter, Amy L. S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title | S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title_full | S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title_fullStr | S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title_full_unstemmed | S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title_short | S region sequence, RNA polymerase II, and histone modifications create chromatin accessibility during class switch recombination |
title_sort | s region sequence, rna polymerase ii, and histone modifications create chromatin accessibility during class switch recombination |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2722165/ https://www.ncbi.nlm.nih.gov/pubmed/19596805 http://dx.doi.org/10.1084/jem.20081678 |
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