Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

Bao, Beier; He, Yingzi; Tang, Dongmei; Li, Wenyan; Li, Huawei

doi:10.3389/fnmol.2017.00051

Cited by 19 publications

(12 citation statements)

References 73 publications

(109 reference statements)

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“…Due to the role histone modifications play during regeneration and reprogramming in other systems [41,78,79], we investigated if the patterns and levels of H3K27me3, H3K4me3, and H3K27Ac were modified at 3 dPR in the new NE originated from the rRPE. Concomitantly with the reduction of 5mC, H3K27me3 decreased significantly in the new NE compared with non-reprogrammed RPE (compare H3K27me3 signal in pigmented vs non-pigmented cells) ( Figure 7b-f and s, Figure S5b-d).…”

Section: Decreased Levels Of H3k27me3 Correlate With Increased Levelsmentioning

confidence: 99%

DNA demethylation is a driver for chick retina regeneration

et al. 2020

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Cellular reprogramming resets the epigenetic landscape to drive shifts in transcriptional programmes and cell identity. The embryonic chick can regenerate a complete neural retina, after retinectomy, via retinal pigment epithelium (RPE) reprogramming in the presence of FGF2. In this study, we systematically analysed the reprogramming competent chick RPE prior to injury, and during different stages of reprogramming. In addition to changes in the expression of genes associated with epigenetic modifications during RPE reprogramming, we observed dynamic changes in histone marks associated with bivalent chromatin (H3K27me3/H3K4me3) and intermediates of the process of DNA demethylation including 5hmC and 5caC. Comprehensive analysis of the methylome by whole-genome bisulphite sequencing (WGBS) confirmed extensive rearrangements of DNA methylation patterns including differentially methylated regions (DMRs) found at promoters of genes associated with chromatin organization and fibroblast growth factor production. We also identified Tet methylcytosine dioxygenase 3 (TET3) as an important factor for DNA demethylation and retina regeneration, capable of reprogramming RPE in the absence of exogenous FGF2. In conclusion, we demonstrate that injury early in RPE reprogramming triggers genome-wide dynamic changes in chromatin, including bivalent chromatin and DNA methylation. In the presence of FGF2, these dynamic modifications are further sustained in the commitment to form a new retina. Our findings reveal active DNA demethylation as an important process that may be applied to remove the epigenetic barriers in order to regenerate retina in mammals.

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Section: Decreased Levels Of H3k27me3 Correlate With Increased Levelsmentioning

confidence: 99%

DNA demethylation is a driver for chick retina regeneration

et al. 2020

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“…ERK functions in the control of cell division, JNK is a critical regulator of transcription and p38 is a key modulator of inflammatory cytokines . Bao et al have confirmed that GSK‐J4 administration inhibited ERK signalling in neuromast cells, while Turgeon et al demonstrated that decreased H3K27 di‐trimethylation affected JNK and p38 phosphorylation in response to IL‐1β in intestinal epithelial cells. Herein, we demonstrated that GSK‐J4 treatment suppressed phosphorylation of Akt and JNK in PDGF‐treated ASMCs, whereas no impact was observed on the phosphorylation of p38 or ERK.…”

Section: Discussionmentioning

confidence: 99%

“…[9][10][11][12][13] Previous studies have demonstrated the important role of H3K27me3 demethylation in the differentiation and reprogramming of numerous cells, including immune cells (dendritic cells and macrophages) 14,15 and structural cells (neurons and epithelial cells). [16][17][18] This event has also been confirmed to have a role in the cellular phenotype transformation known as epithelial-mesenchymal transition (EMT). 19 However, its contribution to the phenotype switch of ASMCs observed in asthma remains obscure.…”

Section: Introductionmentioning

confidence: 90%

“…Histone 3 Lys27 (H3K27) trimethylation (H3K27me3) is believed to dynamically repress gene transcription, whereas H3K27me3 demethylation by specific demethylases, Jumonji C domain containing protein 3 (JMJD3, also termed KDM6B) and ubiquitously transcribed X chromosome tetratricopeptide repeat protein (UTX), is thought to activate gene transcription . Previous studies have demonstrated the important role of H3K27me3 demethylation in the differentiation and reprogramming of numerous cells, including immune cells (dendritic cells and macrophages) and structural cells (neurons and epithelial cells) . This event has also been confirmed to have a role in the cellular phenotype transformation known as epithelial–mesenchymal transition (EMT) .…”

Section: Introductionmentioning

confidence: 99%

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Inhibition of H3K27me3 demethylases attenuates asthma by reversing the shift in airway smooth muscle phenotype

Zhao

et al. 2018

Clin Experimental Allergy

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“…Due to the role histone modifications play during regeneration and reprogramming in other systems [41,63,64], we investigated if the patterns and levels of H3K27me3, H3K4me3, and…”

Section: Decreased Levels Of H3k27me3 Correlates With Increased Levelmentioning

confidence: 99%

DNA demethylation is a driver for chick retina regeneration

Luz-Madrigal

Grajales-Esquivel

Tangeman

et al. 2019

Preprint

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ABSTRACTBackgroundA promising avenue toward human retina regeneration lies in identifying the factors that promote cellular reprogramming to retinal neurons in organisms able to undergo retina regeneration. The embryonic chick can regenerate a complete neural retina, after retinectomy, via retinal pigment epithelium (RPE) reprogramming in the presence of FGF2. Cellular reprogramming resets the epigenetic landscape to drive shifts in transcriptional programs and cell identity. Here, we systematically analyzed the reprogramming competent chick RPE prior to injury, and during different stages of reprogramming. We examined the dynamic changes in the levels and distribution of histone marks and DNA modifications, as well as conducted a comprehensive analysis of the DNA methylome during this process.ResultsIn addition to changes in the expression of genes associated with epigenetic modifications during RPE reprogramming, we observed dynamic changes in histone marks and intermediates of the process of DNA demethylation. At early times after injury, H3K27me3 and 5mC repression marks decreased while 5caC and the H3K4me3 activation mark increased, suggesting genome-wide changes in the bivalent chromatin, impaired DNA methylation, and active DNA demethylation in the chromatin reconfiguration of reprogramming RPE. Comprehensive analysis of the methylome by whole-genome bisulfite sequencing (WGBS) confirmed extensive rearrangements of DNA methylation patterns including differentially methylated regions (DMRs) found at promoters of genes associated with chromatin organization and fibroblast growth factor production. In contrast, genes associated with early RPE reprogramming are hypomethylated in the intact RPE and remain hypomethylated during the process. During the generation of a neuroepithelium (NE) at later stages of reprogramming, decreased levels of H3K27me3, 5mC, and 5hmC coincide with elevated levels of H3K27Ac and 5caC, indicating an active demethylation process and genome-wide changes in the active regulatory landscape. Finally, we identify Tet methylcytosine dioxygenase 3 (TET3) as an important factor for DNA demethylation and retina regeneration in the embryonic chick, capable of reprogramming RPE in the absence of exogenous FGF2.ConclusionOur results demonstrated that injury signals early in RPE reprogramming trigger genome-wide dynamic changes in chromatin, including bivalent chromatin and DNA methylation. In the presence of FGF2 these dynamic modifications are further sustained in the commitment to form a new retina. We identify DNA demethylation as a key process driving the process of RPE reprogramming and identified TET3 as a factor able to reprogram RPE in absence of FGF2. Our findings reveal active DNA demethylation as an important process that may be applied to remove the epigenetic barriers in order to regenerate retina in mammals.

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Inhibition of H3K27me3 Histone Demethylase Activity Prevents the Proliferative Regeneration of Zebrafish Lateral Line Neuromasts

Cited by 19 publications

References 73 publications

DNA demethylation is a driver for chick retina regeneration

DNA demethylation is a driver for chick retina regeneration

Inhibition of H3K27me3 demethylases attenuates asthma by reversing the shift in airway smooth muscle phenotype

DNA demethylation is a driver for chick retina regeneration

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