Somatic hypermutation spectra are independent of the local transcriptional and epigenetic landscape
Schoeberl, U. E.; Fitz, J.; Froussios, K.; Valieris, R.; Makharova, M.; Ourailidis, I.; Bauer, B.; Neumann, T.; Wiedemann, E.-M.; Steininger, M.; Garcia, A. C.; Mastrovito, M.; Mouquet, H.; Silva, I.; Pavri, R.
Show 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.
Matching journals
The top 4 journals account for 50% of the predicted probability mass.
Similar papers in this journal
Similar papers in this journal
Similar papers in this journal
- Chromatin conformation dynamics during CD4+ T cell activation implicates autoimmune disease-associated genes and regulatory elements 96%
- Hierarchical sequence-affinity landscapes shape the evolution of breadth in an anti-influenza receptor binding site antibody 96%
- Live-cell single-molecule tracking highlights requirements for stable Smc5/6 chromatin association in vivo 95%
Similar papers in this journal
- Genomic patterns of transcription-replication interactions in mouse primary B cells 96%
- Activation-induced deaminase is critical for the establishment of DNA methylation patterns prior to the germinal center reaction 96%
- Recruitment of Homodimeric Proneural Factors by Conserved CAT-CAT E-Boxes Drives Major Epigenetic Reconfiguration in Cortical Neurogenesis 95%
Similar papers in this journal
- Single-cell immune profiling reveals novel thymus-seeding populations, T cell commitment, and multi-lineage development in the human thymus 95%
- Polymorphic KIR3DL3 expression modulates tissue-resident and innate-like T cells. 95%
- Quality of vaccination-induced T cell responses is conveyed by polyclonality and high, but not maximum, antigen receptor avidity 94%
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.