ArticleMolecular and cellular biology2012
Nucleosome stability dramatically impacts the targeting of somatic hypermutation.
Article in Molecular and cellular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
11 citing papers in PubMed, 26 citations in OpenAlex.
- Activation-induced cytidine deaminase an antibody diversification enzyme interacts with chromatin modifier UBN1 in B-cells.Scientific reports · 2023Article
- Correlations in Somatic Hypermutation Between Sites in IGHV Genes Can Be Explained by Interactions Between AID and/or Polη Hotspots.Frontiers in immunology · 2020Article
- Article
- Histone H3.3 promotes IgV gene diversification by enhancing formation of AID-accessible single-stranded DNA.The EMBO journal · 2016Article
- Theoretical estimates of exposure timescales of protein binding sites on DNA regulated by nucleosome kinetics.Nucleic acids research · 2016Article
- Article
- Overlapping hotspots in CDRs are critical sites for V region diversification.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Nucleosome positioning and kinetics near transcription-start-site barriers are controlled by interplay between active remodeling and DNA sequence.Nucleic acids research · 2014Article
- AID and Apobec3G haphazard deamination and mutational diversity.Cellular and molecular life sciences : CMLS · 2013Review
- The AID-induced DNA damage response in chromatin.Molecular cell · 2013Review
- Accumulation of the FACT complex, as well as histone H3.3, serves as a target marker for somatic hypermutation.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Somatic hypermutation (SHM) of immunoglobulin (Ig) genes is initiated by the activation-induced cytidine deaminase (AID). However, the influence of chromatin on SHM remains enigmatic. Our previous cell-free studies indicated that AID cannot access nucleosomal DNA in the absence of transcription. We have now investigated the influence of nucleosome stability on mutability in vivo. We introduced two copies of a high-affinity nucleosome positioning sequence (MP2) into a variable Ig gene region to assess its impact on SHM in vivo. The MP2 sequence significantly reduces the mutation frequency throughout the nucleosome, and especially near its center, despite proportions of AID hot spots similar to those in Ig genes. A weak positioning sequence (M5) was designed based on rules deduced from published whole-genome analyses. Replacement of MP2 with M5 resulted in much higher mutation rates throughout the nucleosome. This indicates that both nucleosome stability and positioning significantly influence the SHM pattern. We postulate that, unlike RNA polymerase, AID has reduced access to stable nucleosomes. This study outlines the limits of nucleosome positioning for SHM of Ig genes and suggests that stable nucleosomes may need to be disassembled for access of AID. Possibly the variable regions of Ig genes have evolved for low nucleosome stability to enhance access to AID, DNA repair factors, and error-prone polymerases and, hence, to maximize variability.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.