Evidence map›Paper›PMID 27220848›Full record

ArticleThe EMBO journal2016

Histone H3.3 promotes IgV gene diversification by enhancing formation of AID-accessible single-stranded DNA.

Marina Romanello, Davide Schiavone, Alexander Frey, Julian E Sale

Open access · hybridAbstract read
In one paragraph

Article in The EMBO journal, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.

0numbers the graph read from it
0cells of the map it votes in
18citing papers in PubMed
3.3field-weighted citation impact, top 8% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

18 citing papers in PubMed, 27 citations in OpenAlex.

  1. Article
  2. Article
  3. The role of HIRA-dependent H3.3 deposition and its modifications in the somatic hypermutation of immunoglobulin variable regions.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  4. Article
  5. Role of Dot1L and H3K79 methylation in regulating somatic hypermutation of immunoglobulin genes.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 1 institution in 1 country.

Marina RomanelloMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Davide SchiavoneMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Alexander FreyMedical Research Council Laboratory of Molecular Biology, Cambridge, UK.
Julian E SaleMedical Research Council Laboratory of Molecular Biology, Cambridge, UK jes@mrc-lmb.cam.ac.uk.ORCID 0000-0002-5031-3780
MRC Laboratory of Molecular Biology · GB

Funding

Medical Research Council MC_U105178808Medical Research Council U105178808
6 · The paper itself

Abstract

Immunoglobulin diversification is driven by activation-induced deaminase (AID), which converts cytidine to uracil within the Ig variable (IgV) regions. Central to the recruitment of AID to the IgV genes are factors that regulate the generation of single-stranded DNA (ssDNA), the enzymatic substrate of AID Here, we report that chicken DT40 cells lacking variant histone H3.3 exhibit reduced IgV sequence diversification. We show that this results from impairment of the ability of AID to access the IgV genes due to reduced formation of ssDNA during IgV transcription. Loss of H3.3 also diminishes IgV R-loop formation. However, reducing IgV R-loops by RNase HI overexpression in wild-type cells does not affect IgV diversification, showing that these structures are not necessary intermediates for AID access. Importantly, the reduction in the formation of AID-accessible ssDNA in cells lacking H3.3 is independent of any effect on the level of transcription or the kinetics of RNAPII elongation, suggesting the presence of H3.3 in the nucleosomes of the IgV genes increases the chances of the IgV DNA becoming single-stranded, thereby creating an effective AID substrate.

Indexed as

AICDA (Activation-Induced Cytidine Deaminase)AnimalsCell LineChickensCytidine DeaminaseDNA, Single-StrandedHistonesImmunoglobulin Variable RegionAICDA (Activation-Induced Cytidine Deaminase)Cytidine DeaminaseDNA, Single-StrandedHistonesImmunoglobulin Variable Regionactivation‐induced deaminase (AID)histone H3.3immunoglobulin diversificationsingle‐stranded DNAtranscription

Identifiers

PMID27220848
PMCPMC4883027
OpenAlexW2394692813

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.