Evidence map›Paper›PMID 41135527›Full record

ArticleStem cell reports2025

METTL3 uncouples chromatin accessibility from transcription during retinal development.

Jing Xu, Yuanhao Huang, Zhaowei Han, Qiang Li, Jie Liu, Rajesh C Rao

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

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

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors.

Jing XuDepartment of Ophthalmology & Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall St., Ann Arbor, MI 48105, USA.
Yuanhao HuangDepartment and Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Zhaowei HanDepartment and Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Qiang LiDepartment and Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA.
Jie LiuDepartment and Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA.
Rajesh C RaoDepartment of Ophthalmology & Visual Sciences, W.K. Kellogg Eye Center, University of Michigan, 1000 Wall St., Ann Arbor, MI 48105, USA; Department and Center of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, MI, USA; Department of Pathology, University of Michigan, Ann Arbor, MI, USA; Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; Comprehensive Cancer Center, University of Michigan, Ann Arbor, MI, USA; A. Alfred Taubman Medical Research Institute, University of Michigan, Ann Arbor, MI, USA; Center for RNA Biomedicine, University of Michigan, Ann Arbor, MI, USA; Division of Ophthalmology, Surgery Section, VA Ann Arbor Health System, Ann Arbor, MI, USA. Electronic address: rajeshr@med.umich.edu.

Funding

Molecular Determinants for WDR5-Driven Transcriptional Regulation at Lineage-Specifying Genes During RetinogenesisR01EY030989 · NEI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI RAO, RAJESH C. · 2020 to 2024
$2.2M
Joint analysis of 3D chromatin organization and 1D epigenomeR35HG011279 · NHGRI · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LIU, JIE · 2020 to 2024
$2.1M
NEI NIH HHS R01 EY030989NHGRI NIH HHS R35 HG011279
6 · The paper itself

Abstract

METTL3 is a key regulator of RNA metabolism, yet its genomic and epitranscriptomic roles in tissue development are largely unexplored. Using embryonic stem cell-derived 3D retinal organoids to model retinal progenitor cell (RPC) differentiation, we integrated transcriptome-wide m6A profiling (GLORI), protein-DNA (chromatin immunoprecipitation sequencing [ChIP-seq] and CUT&RUN) and chromatin accessibility (ATAC-seq) mapping, and targeted m6A engineering (dCas13b-FTO) to dissect METTL3 function. Loss of METTL3 nuclear m6A activity disrupted Rx+ retinal anlage formation in vitro, with dCas13b-FTO epitranscriptome engineering revealing that m6A at the Six3 3'UTR governs its stability. Surprisingly, while METTL3 loss altered histone modifications and chromatin accessibility, its direct chromatin targets showed little transcriptional correlation. A degron-based METTL3 degradation strategy, paired with protein-RNA interaction profiling, exposed rapid regulatory shifts in RPCs, revealing a METTL3-Ythdf1 protein-RNA axis. Our multi-omics approach establishes METTL3-dependent m6A as a critical epitranscriptomic layer in retinal development, unveiling a genomic paradigm in which chromatin accessibility diverges from transcriptional output.

Indexed as

ChromatinMethyltransferasesRetinaTranscription, GeneticAnimalsCell DifferentiationGene Expression Regulation, DevelopmentalMiceChromatinMethyltransferasesMettl3 protein, mouseCas13bepigeneticsepitranscriptomicsFTOm6AMETTL3organoidretinaRNA methylationstem cells

Identifiers

PMID41135527
PMCPMC12790738

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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.