Somatic hypermutation patterns in immunoglobulin variable regions are established independently of the local transcriptional landscape
Somatic hypermutation patterns in immunoglobulin variable regions are established independently of the local transcriptional landscape
Abstract Somatic hypermutation (SHM) of immunoglobulin variable (V) regions modulates antibody-antigen affinity is initiated by activation-induced cytidine deaminase (AID) on single-stranded DNA (ssDNA). Transcription is essential for SHM and AID target genes harbor activating chromatin marks and RNA polymerase II (Pol II) stalling, leading to the model that these features favor higher rates of mutagenesis. However, whether such relationships exist within V regions is undetermined. Here, we directly compared SHM and nascent transcription across four V regions and 275 non-immunoglobulin SHM targets at single-nucleotide resolution using precision run-on sequencing (PRO-seq). Although locales of Pol II enrichment and zones of Pol II stalling were detected within V regions, their correlation with SHM was not statistically significant. Moreover, SHM was robust against major reductions of activating epigenetic marks and transcription. This data suggests that SHM patterns and spectra are established independently of specific local nascent transcriptional features.
Pavri Rushad、Schoeberl Ursula E.、Fitz Johanna、Bauer Bernd、Wiedemann Eva-Maria、Steininger Monika、Mouquet Hugo、Da Silva Israel Tojal、Neumann Tobias、Garcia Adriana Cantoran、Mastrovito Marialaura、Froussios Kimon、Valieris Renan、Ourailidis Iordanis、Makharova Marina
Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Laboratory of Humoral Immunology, Institut Pasteur, INSERM U1222, Universit¨| Paris Cit¨|Laboratory of Bioinformatics and Computational Biology, A. C. Camargo Cancer CenterResearch Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)Laboratory of Bioinformatics and Computational Biology, A. C. Camargo Cancer CenterResearch Institute of Molecular Pathology (IMP)Research Institute of Molecular Pathology (IMP)
遗传学分子生物学
Pavri Rushad,Schoeberl Ursula E.,Fitz Johanna,Bauer Bernd,Wiedemann Eva-Maria,Steininger Monika,Mouquet Hugo,Da Silva Israel Tojal,Neumann Tobias,Garcia Adriana Cantoran,Mastrovito Marialaura,Froussios Kimon,Valieris Renan,Ourailidis Iordanis,Makharova Marina.Somatic hypermutation patterns in immunoglobulin variable regions are established independently of the local transcriptional landscape[EB/OL].(2025-03-28)[2025-04-27].https://www.biorxiv.org/content/10.1101/2022.05.21.492925.点此复制
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