Evidence map›Paper›PMID 40148869›Full record

ArticleEpigenetics & chromatin2025

Mechanism of non-coding RNA regulation of DNMT3A.

Jonathan E Sandoval, Nancy V N Carullo, Aaron J Salisbury, Jeremy J Day, Norbert O Reich

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Article in Epigenetics & chromatin, 2025. 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

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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

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

5 authors.

Jonathan E SandovalDepartment of Molecular, Cellular and Developmental Biology, University of California, Santa Barbara, CA, 93106-9510, USA.
Nancy V N CarulloDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Aaron J SalisburyDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Jeremy J DayDepartment of Neurobiology, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
Norbert O ReichDepartment of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106-9510, USA. reich@chem.ucsb.edu.

Funding

The National Science Foundation (NSF) 1808775
6 · The paper itself

Abstract

backgroundDe novo DNA methylation by DNMT3A is a fundamental epigenetic modification for transcriptional regulation. Histone tails and regulatory proteins regulate DNMT3A, and the crosstalk between these epigenetic mechanisms ensures appropriate DNA methylation patterning. Based on findings showing that Fos ecRNA inhibits DNMT3A activity in neurons, we sought to characterize the contribution of this regulatory RNA in the modulation of DNMT3A in the presence of regulatory proteins and histone tails.

resultsWe show that Fos ecRNA and mRNA strongly correlate in primary cortical neurons on a single cell level and provide evidence that Fos ecRNA modulation of DNMT3A at these actively transcribed sites occurs in a sequence-independent manner. Further characterization of the Fos ecRNA-DNMT3A interaction showed that Fos-1 ecRNA binds the DNMT3A tetramer interface and clinically relevant DNMT3A substitutions that disrupt the inhibition of DNMT3A activity by Fos-1 ecRNA are restored by the formation of heterotetramers with DNMT3L. Lastly, using DNMT3L and Fos ecRNA in the presence of synthetic histone H3 tails or reconstituted polynucleosomes, we found that regulatory RNAs play dominant roles in the modulation of DNMT3A activity.

conclusionOur results are consistent with a model for RNA regulation of DNMT3A that involves localized production of short RNAs binding to a nonspecific site on the protein, rather than formation of localized RNA/DNA structures. We propose that regulatory RNAs play a dominant role in the regulation of DNMT3A catalytic activity at sites with increased production of regulatory RNAs.

Indexed as

DNA (Cytosine-5-)-MethyltransferasesAnimalsCells, CulturedDNA MethylationDNA Methyltransferase 3AEpigenesis, GeneticHistonesHumansMiceNeuronsProto-Oncogene Proteins c-fosRNA, MessengerDNA (Cytosine-5-)-MethyltransferasesDNA Methyltransferase 3ADNMT3A protein, humanDnmt3a protein, mouseDnmt3l protein, mouseHistonesProto-Oncogene Proteins c-fosRNA, MessengerAllosteryCancerDNA methylationDNA methyltransferase 3A (DNMT3A)DNMT3LEpigeneticsGene regulationProtein-RNA interactions

Identifiers

PMID40148869
PMCPMC11951571

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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.