Evidence map›Paper›PMID 36698218›Full record

ArticleEpigenetics & chromatin2023

Dynamic changes in whole genome DNA methylation, chromatin and gene expression during mouse lens differentiation.

William Chang, Yilin Zhao, Danielle Rayêe, Qing Xie, Masako Suzuki, Deyou Zheng, Ales Cvekl

Open access · goldAbstract read
In one paragraph

Article in Epigenetics & chromatin, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
6.0field-weighted citation impact, top 3% 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

29 citing papers in PubMed, 39 citations in OpenAlex.

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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

7 authors at 1 institution in 1 country.

William ChangDepartment of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Yilin ZhaoGenetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Danielle RayêeDepartment of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Qing XieDepartment of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Masako SuzukiGenetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Deyou ZhengGenetics, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
Ales CveklDepartment of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. ales.cvekl@einsteinmed.edu.
Albert Einstein College of Medicine · US

Funding

WORD PROCESSORP30CA013330 · NCI · YESHIVA UNIVERSITY · PI Ulrich Steidl · 1985 to 2026
$111.2M
PAX-6 AS A KEY REGULATOR OF LENS DEVELOPMENTR01EY012200 · NEI · YESHIVA UNIVERSITY · PI CVEKL, ALES · 2000 to 2025
$13.1M
Transcriptional Control of the Mouse aA-crystallin locusR01EY014237 · NEI · YESHIVA UNIVERSITY · PI Ales Cvekl · 2003 to 2026
$11.0M
IMPACT OF PRENATAL VITAMIN A DEFICIENCY ON CELL FATE ALTERATIONS IN ADULT AIRWAY HYPERRESPONSIVENESSR01HL145302 · NHLBI · TEXAS A&M AGRILIFE RESEARCH · PI SUZUKI, MASAKO · 2020 to 2023
$1.6M
NCI NIH HHS P30 CA013330NEI NIH HHS R01 EY012200NEI NIH HHS R01 EY014237NHLBI NIH HHS R01 HL145302
6 · The paper itself

Abstract

backgroundCellular differentiation is marked by temporally and spatially coordinated gene expression regulated at multiple levels. DNA methylation represents a universal mechanism to control chromatin organization and its accessibility. Cytosine methylation of CpG dinucleotides regulates binding of methylation-sensitive DNA-binding transcription factors within regulatory regions of transcription, including promoters and distal enhancers. Ocular lens differentiation represents an advantageous model system to examine these processes as lens comprises only two cell types, the proliferating lens epithelium and postmitotic lens fiber cells all originating from the epithelium.

resultsUsing whole genome bisulfite sequencing (WGBS) and microdissected lenses, we investigated dynamics of DNA methylation and chromatin changes during mouse lens fiber and epithelium differentiation between embryos (E14.5) and newborns (P0.5). Histone H3.3 variant chromatin landscapes were also generated for both P0.5 lens epithelium and fibers by chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq). Tissue-specific features of DNA methylation patterns are demonstrated via comparative studies with embryonic stem (ES) cells and neural progenitor cells (NPCs) at Nanog, Pou5f1, Sox2, Pax6 and Six3 loci. Comparisons with ATAC-seq and RNA-seq data demonstrate that reduced methylation is associated with increased expression of fiber cell abundant genes, including crystallins, intermediate filament (Bfsp1 and Bfsp2) and gap junction proteins (Gja3 and Gja8), marked by high levels of histone H3.3 within their transcribed regions. Interestingly, Pax6-binding sites exhibited predominantly DNA hypomethylation in lens chromatin. In vitro binding of Pax6 proteins showed Pax6's ability to interact with sites containing one or two methylated CpG dinucleotides.

conclusionsOur study has generated the first data on methylation changes between two different stages of mammalian lens development and linked these data with chromatin accessibility maps, presence of histone H3.3 and gene expression. Reduced DNA methylation correlates with expression of important genes involved in lens morphogenesis and lens fiber cell differentiation.

Indexed as

ChromatinHistonesLens, CrystallineAnimalsCell DifferentiationDNADNA MethylationGene ExpressionMiceChromatinDNAHistonesATAC-seqDifferentiationDNA methylationGene regulationHistone H3.3LensOpen chromatinPax6RNA-seq

Identifiers

PMID36698218
PMCPMC9875507
OpenAlexW4317932792

What OpenQuestion holds

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LicenceCC BY
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.