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DNA demethylation is a driver for chick retina regeneration
Agustín Luz-Madrigal1,2, Erika Grajales-Esquivel1, Jared Tangeman1
1Department of Biology and Center for Visual Sciences at Miami University, Miami University , Oxford, OH, USA.
Epigenetics
|April 16, 2020
Summary
Cellular reprogramming in chick retinal pigment epithelium (RPE) involves dynamic epigenetic changes, including DNA demethylation. Tet methylcytosine dioxygenase 3 (TET3) is crucial for this process and retina regeneration, offering potential for mammalian retina repair.
Area of Science:
- Epigenetics and Developmental Biology
- Cellular Reprogramming
- Regenerative Medicine
Background:
- Cellular reprogramming resets epigenetic landscapes, altering cell identity and gene expression.
- The embryonic chick retina can regenerate via retinal pigment epithelium (RPE) reprogramming.
- Fibroblast growth factor 2 (FGF2) is known to facilitate RPE reprogramming.
Purpose of the Study:
- To systematically analyze epigenetic modifications in chick RPE before and during reprogramming.
- To identify key molecular factors involved in RPE reprogramming and retina regeneration.
- To explore the potential of DNA demethylation for mammalian retina regeneration.
Main Methods:
- Analysis of gene expression and histone marks (H3K27me3/H3K4me3) during RPE reprogramming.
- Whole-genome bisulphite sequencing (WGBS) for comprehensive methylome analysis.
- Identification and functional assessment of Tet methylcytosine dioxygenase 3 (TET3).
Main Results:
- Dynamic changes in histone marks and DNA demethylation intermediates (5hmC, 5caC) were observed.
- WGBS revealed extensive DNA methylation rearrangements, with differentially methylated regions (DMRs) at specific gene promoters.
- TET3 was identified as a key factor for DNA demethylation and RPE reprogramming, even without FGF2.
Conclusions:
- Injury-induced RPE reprogramming triggers genome-wide chromatin dynamics, including bivalent chromatin and DNA methylation.
- FGF2 sustains these modifications, promoting new retina formation.
- Active DNA demethylation is a critical process for overcoming epigenetic barriers in retina regeneration, with potential applications in mammals.
