TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells.
Ten-Eleven-Translocase (TET) enzymes contribute to the regulation of the methylome via successive oxidation of 5-methyl cytosine (5mC) to derivatives which can be actively removed by base-excision-repair (BER) mechanisms in the absence of cell division. This is particularly important in post-mitotic...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294187&type=printable |
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| author | Valeria Leon Kropf Caraugh J Albany Anna Zoccarato Hannah L H Green Youwen Yang Alison C Brewer |
| author_facet | Valeria Leon Kropf Caraugh J Albany Anna Zoccarato Hannah L H Green Youwen Yang Alison C Brewer |
| author_sort | Valeria Leon Kropf |
| collection | DOAJ |
| description | Ten-Eleven-Translocase (TET) enzymes contribute to the regulation of the methylome via successive oxidation of 5-methyl cytosine (5mC) to derivatives which can be actively removed by base-excision-repair (BER) mechanisms in the absence of cell division. This is particularly important in post-mitotic neurons where changes in DNA methylation are known to associate with changes in neural function. TET3, specifically, is a critical regulator of both neuronal differentiation in development and mediates dynamic changes in the methylome of adult neurons associated with cognitive function. While DNA methylation is understood to regulate transcription, little is known of the specific targets of TET3-dependent catalytic activity in neurons. We report the results of an unbiased transcriptome analysis of the neuroblastoma-derived cell line; Neuro2A, in which Tet3 was silenced. Oxidative phosphorylation (OxPhos) was identified as the most significantly down-regulated functional canonical pathway, and these findings were confirmed by measurements of oxygen consumption rate in the Seahorse bioenergetics analyser. The mRNA levels of both nuclear- and mitochondrial-encoded OxPhos genes were reduced by Tet3-silencing, but we found no evidence for differential (hydroxy)methylation deposition at these gene loci. However, the mRNA expression of genes known to be involved in mitochondrial quality control were also shown to be significantly downregulated in the absence of TET3. One of these genes; EndoG, was identified as a direct target of TET3-catalytic activity at non-CpG methylated sites within its gene body. Accordingly, we propose that aberrant mitochondrial homeostasis may contribute to the decrease in OxPhos, observed upon Tet3-downregulation in Neuro2A cells. |
| first_indexed | 2024-03-07T16:28:49Z |
| format | Article |
| id | doaj.art-b054a4a5089743088870f619cb133958 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-03-07T16:28:49Z |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-b054a4a5089743088870f619cb1339582024-03-03T12:56:28ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-01191e029418710.1371/journal.pone.0294187TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells.Valeria Leon KropfCaraugh J AlbanyAnna ZoccaratoHannah L H GreenYouwen YangAlison C BrewerTen-Eleven-Translocase (TET) enzymes contribute to the regulation of the methylome via successive oxidation of 5-methyl cytosine (5mC) to derivatives which can be actively removed by base-excision-repair (BER) mechanisms in the absence of cell division. This is particularly important in post-mitotic neurons where changes in DNA methylation are known to associate with changes in neural function. TET3, specifically, is a critical regulator of both neuronal differentiation in development and mediates dynamic changes in the methylome of adult neurons associated with cognitive function. While DNA methylation is understood to regulate transcription, little is known of the specific targets of TET3-dependent catalytic activity in neurons. We report the results of an unbiased transcriptome analysis of the neuroblastoma-derived cell line; Neuro2A, in which Tet3 was silenced. Oxidative phosphorylation (OxPhos) was identified as the most significantly down-regulated functional canonical pathway, and these findings were confirmed by measurements of oxygen consumption rate in the Seahorse bioenergetics analyser. The mRNA levels of both nuclear- and mitochondrial-encoded OxPhos genes were reduced by Tet3-silencing, but we found no evidence for differential (hydroxy)methylation deposition at these gene loci. However, the mRNA expression of genes known to be involved in mitochondrial quality control were also shown to be significantly downregulated in the absence of TET3. One of these genes; EndoG, was identified as a direct target of TET3-catalytic activity at non-CpG methylated sites within its gene body. Accordingly, we propose that aberrant mitochondrial homeostasis may contribute to the decrease in OxPhos, observed upon Tet3-downregulation in Neuro2A cells.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294187&type=printable |
| spellingShingle | Valeria Leon Kropf Caraugh J Albany Anna Zoccarato Hannah L H Green Youwen Yang Alison C Brewer TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. PLoS ONE |
| title | TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. |
| title_full | TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. |
| title_fullStr | TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. |
| title_full_unstemmed | TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. |
| title_short | TET3 is a positive regulator of mitochondrial respiration in Neuro2A cells. |
| title_sort | tet3 is a positive regulator of mitochondrial respiration in neuro2a cells |
| url | https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0294187&type=printable |
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