Expression patterns of dnmt3aa, dnmt3ab, and dnmt4 during development and fin regeneration in zebrafish

Takayama, Kazuya; Shimoda, Nobuyoshi; Takanaga, Shunsuke; Hozumi, Shunya; Kikuchi, Yutaka

doi:10.1016/j.gep.2014.01.005

Cited by 53 publications

(43 citation statements)

References 29 publications

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“…In addition, dnmt4 is also expressed in the tectum, dorsal and ventral thalamus, and in the pallium region. 75 dnmt5 expression has also been identified throughout the anterior zebrafish embryo with expression localizing to the ciliary marginal zone of the retina by 72 hpf. 76 …”

Section: Discussionmentioning

confidence: 99%

Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression

Wirbisky-Hershberger

Sánchez

Horzmann

et al. 2017

Food and Chemical Toxicology

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Atrazine, a herbicide used on agricultural crops is widely applied in the Midwestern United States as well as other areas of the globe. Atrazine frequently contaminates potable water supplies and is a suspected endocrine disrupting chemical. Previous studies have reported morphological, hormonal, and molecular alterations due to developmental and adulthood atrazine exposure; however, studies examining epigenetic alterations are limited. In this study, the effects of atrazine exposure on DNA methyltransferase (DNMT) activity and kinetics were evaluated. Global DNA methylation levels and dnmt expression in zebrafish larvae exposed to 0, 3, or 30 parts per billion (ppb) atrazine throughout embryogenesis was then assessed. Results indicate that atrazine significantly decreased the activity of maintenance DNMTs and that the inhibition mechanism can be described using non-competitive Michaelis-Menten kinetics. Furthermore, results show that an embryonic atrazine exposure decreases global methylation levels and the expression of dnmt4 and dnmt5. These findings indicate that atrazine exposure can decrease the expression and activity of DNMTs, leading to decreased DNA methylation levels.

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Section: Discussionmentioning

confidence: 99%

Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression

Wirbisky-Hershberger

Sánchez

Horzmann

et al. 2017

Food and Chemical Toxicology

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“…This enzyme is traditionally considered a de novo methyltransferase, responsible of initiating methylation of previously unmethylated DNA (Chen et al, 2003). Orthologs to this enzyme have been identified in zebrafish, and are expressed at critical points during development of the lens and retina, particularly in the ciliary marginal zone (CMZ), where they are thought to maintain the proliferative properties of this area (Seritrakul and Gross, 2014; Takayama et al, 2014). While extensive characterization of DNMTs expression in mammalian retina is lacking, there is a report of low levels of these enzymes in MG, when compared with other cell types in the neural retina, which might account for its progenitor-like properties (Nasonkin et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

“…It has been observed that Dnmt3b orthologs are expressed in blastema cells during fin regeneration in zebrafish, following an interesting expression pattern, i.e., they are absent before and immediately after amputation, and then their expression is induced 3 days after damage, suggesting a crucial involvement in the recovery of 5-methyl-cytosine (5 mC) levels (Takayama et al, 2014). Our results resemble these observations.…”

Section: Discussionmentioning

confidence: 99%

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

Reyes-Aguirre

Lamas

2016

Front. Neurosci.

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Müller glia (MG) is the most abundant glial type in the vertebrate retina. Among its many functions, it is capable of responding to injury by dedifferentiating, proliferating, and differentiating into every cell types lost to damage. This regenerative ability is notoriously absent in mammals. We have previously reported that cultured mammalian MG undergoes a partial dedifferentiation, but fails to fully acquire a progenitor phenotype and differentiate into neurons. This might be explained by a mnemonic mechanism comprised by epigenetic traits, such as DNA methylation. To achieve a better understanding of this epigenetic memory, we studied the expression of pluripotency-associated genes, such as Oct4, Nanog, and Lin28, which have been reported as necessary for regeneration in fish, at early times after NMDA-induced retinal injury in a mouse experimental model. We found that although Oct4 is expressed rapidly after damage (4 hpi), it is silenced at 24 hpi. This correlates with a significant decrease in the DNA methyltransferase Dnmt3b expression, which returns to basal levels at 24 hpi. By MS-PCR, we observed a decrease in Oct4 methylation levels at 4 and 12 hpi, before returning to a fully methylated state at 24 hpi. To demonstrate that these changes are restricted to MG, we separated these cells using a GLAST antibody coupled with magnetic beads. Finally, intravitreous administration of the DNA-methyltransferase inhibitor SGI-1027 induced Oct4 expression at 24 hpi in MG. Our results suggest that mammalian MG injury-induced dedifferentiation could be restricted by DNA methylation, which rapidly silences Oct4 expression, preventing multipotency acquisition.

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“…6B and C, respectively). It has been suggested that de novo methyltransferases are required for proper tissue regeneration in other animal models (36,37). Thus, it is possible that DNMT3 was recruited as part of the hepatic regeneration between DEN and 16D.…”

Section: Discussionmentioning

confidence: 99%

DNA methyltransferases 3a and 3b are differentially expressed in the early stages of a rat liver carcinogenesis model

et al. 2014

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Carcinogenesis is driven by the accumulation of mutations and abnormal DNA methylation patterns, particularly the hypermethylation of tumor‑suppressor genes. Changes in genomic DNA methylation patterns are established by the DNA methyltransferases (DNMTs) family: DNMT1, DNMT3a and DNMT3b. The DNMTs are known to be overexpressed in tumors. However, when the DNMTs expression profile is altered in earlier stages of carcinogenesis remains to be elucidated. The resistant hepatocyte model (RHM) allows the analysis of the hepatocellular carcinoma (HCC) from the formation of altered cell foci to the appearance of tumors in rats. To investigate the DNMTs expression in this model, we first observed that timp3, rassf1a and p16 genes became methylated during cancer development by methylation‑specific PCR (MSP) and the bisulphate sequencing PCR (BSP) of timp3. The differential expression at the RNA and protein level of the three DNMTs was also assessed. dnmt1 expression was higher in tumors than in normal and early cancer stages. However, no evident overexpression of the enzyme was identified by immunohistochemistry. By contrast, DNMT3a and DNMT3b were consistently subexpressed in tumors. In the present study, we report a carcinogenesis model that does not feature the overexpression of DNMT1 but exhibits a transient expression of DNMT3a and DNMT3b.

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Expression patterns of dnmt3aa, dnmt3ab, and dnmt4 during development and fin regeneration in zebrafish

Cited by 53 publications

References 29 publications

Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression

Atrazine exposure decreases the activity of DNMTs, global DNA methylation levels, and dnmt expression

Oct4 Methylation-Mediated Silencing As an Epigenetic Barrier Preventing Müller Glia Dedifferentiation in a Murine Model of Retinal Injury

DNA methyltransferases 3a and 3b are differentially expressed in the early stages of a rat liver carcinogenesis model

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