Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity
Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking ma...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2017-01-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2016.1253651 |
| _version_ | 1797678964537294848 |
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| author | Thanh V. Hoang Evan R. Horowitz Blake R. Chaffee Peipei Qi Rachel E. Flake Devin G. Bruney Blake J. Rasor Savana E. Rosalez Brad D. Wagner Michael L. Robinson |
| author_facet | Thanh V. Hoang Evan R. Horowitz Blake R. Chaffee Peipei Qi Rachel E. Flake Devin G. Bruney Blake J. Rasor Savana E. Rosalez Brad D. Wagner Michael L. Robinson |
| author_sort | Thanh V. Hoang |
| collection | DOAJ |
| description | Despite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected. The simultaneous deletion of phosphatase and tensin homolog (Pten) elevated the level of phosphorylated AKT and rescued many of the morphological defects and cell death in DNMT1-deficient lenses. With a different Cre driver (MLR10) we demonstrated that a small number of lens epithelial cells escaped Dnmt1-deletion and over-proliferated to compensate for the loss of Dnmt1-deleted cells, suggesting that lens epithelium possess a substantial capacity for self-renewal. Unlike lenses deficient for Dnmt1, inactivation of both Dnmt3a and Dnmt3b by either the Le-Cre or MLR10-Cre transgene did not result in any obvious lens phenotype prior to 10 months of age. Taken together, while lens epithelial cell survival requires DNMT1, morphologically normal lenses develop in the absence of both DNMT3A and DNMT3B. |
| first_indexed | 2024-03-11T23:07:31Z |
| format | Article |
| id | doaj.art-7ec74e0ab97e473d8d67c82d20d0cd1a |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:31Z |
| publishDate | 2017-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-7ec74e0ab97e473d8d67c82d20d0cd1a2023-09-21T12:43:12ZengTaylor & Francis GroupEpigenetics1559-22941559-23082017-01-01121274010.1080/15592294.2016.12536511253651Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activityThanh V. Hoang0Evan R. Horowitz1Blake R. Chaffee2Peipei Qi3Rachel E. Flake4Devin G. Bruney5Blake J. Rasor6Savana E. Rosalez7Brad D. Wagner8Michael L. Robinson9Miami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityMiami UniversityDespite the wealth of knowledge of transcription factors involved in lens development, little information exists about the role of DNA methylation in this process. Here, we investigated the role of DNA methylation in lens development and fiber cell differentiation using mice conditionally lacking maintenance or de novo methyltransferases in the lens lineage. We found that while Dnmt1 inactivation at the lens placode stage (via the Le-Cre transgene) led to lens DNA hypomethylation and severe lens epithelial apoptosis, lens fiber cell differentiation remained largely unaffected. The simultaneous deletion of phosphatase and tensin homolog (Pten) elevated the level of phosphorylated AKT and rescued many of the morphological defects and cell death in DNMT1-deficient lenses. With a different Cre driver (MLR10) we demonstrated that a small number of lens epithelial cells escaped Dnmt1-deletion and over-proliferated to compensate for the loss of Dnmt1-deleted cells, suggesting that lens epithelium possess a substantial capacity for self-renewal. Unlike lenses deficient for Dnmt1, inactivation of both Dnmt3a and Dnmt3b by either the Le-Cre or MLR10-Cre transgene did not result in any obvious lens phenotype prior to 10 months of age. Taken together, while lens epithelial cell survival requires DNMT1, morphologically normal lenses develop in the absence of both DNMT3A and DNMT3B.http://dx.doi.org/10.1080/15592294.2016.1253651developmentdna methylationdnmt1dnmt3adnmt3blens |
| spellingShingle | Thanh V. Hoang Evan R. Horowitz Blake R. Chaffee Peipei Qi Rachel E. Flake Devin G. Bruney Blake J. Rasor Savana E. Rosalez Brad D. Wagner Michael L. Robinson Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity Epigenetics development dna methylation dnmt1 dnmt3a dnmt3b lens |
| title | Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity |
| title_full | Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity |
| title_fullStr | Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity |
| title_full_unstemmed | Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity |
| title_short | Lens development requires DNMT1 but takes place normally in the absence of both DNMT3A and DNMT3B activity |
| title_sort | lens development requires dnmt1 but takes place normally in the absence of both dnmt3a and dnmt3b activity |
| topic | development dna methylation dnmt1 dnmt3a dnmt3b lens |
| url | http://dx.doi.org/10.1080/15592294.2016.1253651 |
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