دورية أكاديمية
Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences.
| العنوان: | Targeting of somatic hypermutation by immunoglobulin enhancer and enhancer-like sequences. |
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| المؤلفون: | Jean-Marie Buerstedde, Jukka Alinikula, Hiroshi Arakawa, Jessica J McDonald, David G Schatz |
| المصدر: | PLoS Biology, Vol 12, Iss 4, p e1001831 (2014) |
| بيانات النشر: | Public Library of Science (PLoS), 2014. |
| سنة النشر: | 2014 |
| المجموعة: | LCC:Biology (General) |
| مصطلحات موضوعية: | Biology (General), QH301-705.5 |
| الوصف: | Somatic hypermutation (SH) generates point mutations within rearranged immunoglobulin (Ig) genes of activated B cells, providing genetic diversity for the affinity maturation of antibodies. SH requires the activation-induced cytidine deaminase (AID) protein and transcription of the mutation target sequence, but how the Ig gene specificity of mutations is achieved has remained elusive. We show here using a sensitive and carefully controlled assay that the Ig enhancers strongly activate SH in neighboring genes even though their stimulation of transcription is negligible. Mutations in certain E-box, NFκB, MEF2, or Ets family binding sites--known to be important for the transcriptional role of Ig enhancers--impair or abolish the activity. Full activation of SH typically requires a combination of multiple Ig enhancer and enhancer-like elements. The mechanism is evolutionarily conserved, as mammalian Ig lambda and Ig heavy chain intron enhancers efficiently stimulate hypermutation in chicken cells. Our results demonstrate a novel regulatory function for Ig enhancers, indicating that they either recruit AID or alter the accessibility of the nearby transcription units. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1544-9173 1545-7885 |
| العلاقة: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24691034/?tool=EBITest; https://doaj.org/toc/1544-9173Test; https://doaj.org/toc/1545-7885Test |
| DOI: | 10.1371/journal.pbio.1001831 |
| الوصول الحر: | https://doaj.org/article/d8c75f8713464da9bd7f8ad340ca1263Test |
| رقم الانضمام: | edsdoj.8c75f8713464da9bd7f8ad340ca1263 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 15449173 15457885 |
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| DOI: | 10.1371/journal.pbio.1001831 |