Evidence map›Paper›PMID 39666677›Full record

ArticlePloS one2024

Modeling the consequences of age-linked rDNA hypermethylation with dCas9-directed DNA methylation in human cells.

Yana Blokhina, Abigail Buchwalter

Abstract read
In one paragraph

Article in PloS one, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
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

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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

1 citing paper in PubMed.

  1. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

2 authors.

Yana BlokhinaCardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, California, United States of America.
Abigail BuchwalterCardiovascular Research Institute and Department of Physiology, University of California, San Francisco, San Francisco, California, United States of America.ORCID 0000-0001-7181-6961

Funding

MOLECULAR AND CELLULAR BASIS OF CARDIOVASCULAR DISEASET32HL007731 · NHLBI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI Brian L Black · 1992 to 2026
$12.4M
NHLBI NIH HHS T32 HL007731
6 · The paper itself

Abstract

Ribosomal DNA (rDNA) genes encode the structural RNAs of the ribosome and are present in hundreds of copies in mammalian genomes. Age-linked DNA hypermethylation throughout the rDNA constitutes a robust "methylation clock" that accurately reports age, yet the consequences of hypermethylation on rDNA function are unknown. We confirmed that pervasive hypermethylation of rDNA occurs during mammalian aging and senescence while rDNA copy number remains stable. We found that DNA methylation is exclusively found on the promoters and gene bodies of inactive rDNA. To model the effects of age-linked methylation on rDNA function, we directed de novo DNA methylation to the rDNA promoter or gene body with a nuclease-dead Cas9 (dCas9)-DNA methyltransferase fusion enzyme in human cells. Hypermethylation at each target site had no detectable effect on rRNA transcription, nucleolar morphology, or cellular growth rate. Instead, human UBF and Pol I remain bound to rDNA promoters in the presence of increased DNA methylation. These data suggest that promoter methylation is not sufficient to impair transcription of the human rDNA and imply that the human rDNA transcription machinery may be resilient to age-linked rDNA hypermethylation.

Indexed as

AgingDNA MethylationDNA, RibosomalPromoter Regions, GeneticAnimalsCRISPR-Associated Protein 9CRISPR-Cas SystemsHumansPol1 Transcription Initiation Complex ProteinsRNA Polymerase ITranscription, GeneticCRISPR-Associated Protein 9DNA, RibosomalPol1 Transcription Initiation Complex ProteinsRNA Polymerase Itranscription factor UBF

Identifiers

PMID39666677
PMCPMC11637357

What OpenQuestion holds

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Registered trials

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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.