Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA
ABSTRACTAltered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Epigenetics |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/15592294.2023.2294516 |
| _version_ | 1797383499660918784 |
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| author | Thu N. A. Doan James M. Cowley Aaron L. Phillips Jessica F. Briffa Shalem Y. Leemaqz Rachel A. Burton Tania Romano Mary E. Wlodek Tina Bianco-Miotto |
| author_facet | Thu N. A. Doan James M. Cowley Aaron L. Phillips Jessica F. Briffa Shalem Y. Leemaqz Rachel A. Burton Tania Romano Mary E. Wlodek Tina Bianco-Miotto |
| author_sort | Thu N. A. Doan |
| collection | DOAJ |
| description | ABSTRACTAltered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman’s ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring. |
| first_indexed | 2024-03-08T21:20:54Z |
| format | Article |
| id | doaj.art-087c2f47fb0c465788e81285c8540942 |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-08T21:20:54Z |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-087c2f47fb0c465788e81285c85409422023-12-21T09:12:20ZengTaylor & Francis GroupEpigenetics1559-22941559-23082024-12-0119110.1080/15592294.2023.2294516Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNAThu N. A. Doan0James M. Cowley1Aaron L. Phillips2Jessica F. Briffa3Shalem Y. Leemaqz4Rachel A. Burton5Tania Romano6Mary E. Wlodek7Tina Bianco-Miotto8School of Agriculture, Food and Wine, & Waite Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaSchool of Agriculture, Food and Wine, & Waite Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaSchool of Agriculture, Food and Wine, & Waite Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Victoria, AustraliaRobinson Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaSchool of Agriculture, Food and Wine, & Waite Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaDepartment of Physiology, Anatomy and Microbiology, La Trobe University, Bundoora, Victoria, AustraliaDepartment of Anatomy and Physiology, The University of Melbourne, Parkville, Victoria, AustraliaSchool of Agriculture, Food and Wine, & Waite Research Institute, University of Adelaide, Adelaide, South Australia, AustraliaABSTRACTAltered epigenetic mechanisms have been previously reported in growth restricted offspring whose mothers experienced environmental insults during pregnancy in both human and rodent studies. We previously reported changes in the expression of the DNA methyltransferase Dnmt3a and the imprinted genes Cdkn1c (Cyclin-dependent kinase inhibitor 1C) and Kcnq1 (Potassium voltage-gated channel subfamily Q member 1) in the kidney tissue of growth restricted rats whose mothers had uteroplacental insufficiency induced on day 18 of gestation, at both embryonic day 20 (E20) and postnatal day 1 (PN1). To determine the mechanisms responsible for changes in the expression of these imprinted genes, we investigated DNA methylation of KvDMR1, an imprinting control region (ICR) that includes the promoter of the antisense long non-coding RNA Kcnq1ot1 (Kcnq1 opposite strand/antisense transcript 1). Kcnq1ot1 expression decreased by 51% in growth restricted offspring compared to sham at PN1. Interestingly, there was a negative correlation between Kcnq1ot1 and Kcnq1 in the E20 growth restricted group (Spearman’s ρ = 0.014). No correlation was observed between Kcnq1ot1 and Cdkn1c expression in either group at any time point. Additionally, there was a 11.25% decrease in the methylation level at one CpG site within KvDMR1 ICR. This study, together with others in the literature, supports that long non-coding RNAs may mediate changes seen in tissues of growth restricted offspring.https://www.tandfonline.com/doi/10.1080/15592294.2023.2294516Intrauterine growth restrictionuteroplacental insufficiencyepigenetic mechanismslong non-coding RNADNA methylation |
| spellingShingle | Thu N. A. Doan James M. Cowley Aaron L. Phillips Jessica F. Briffa Shalem Y. Leemaqz Rachel A. Burton Tania Romano Mary E. Wlodek Tina Bianco-Miotto Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA Epigenetics Intrauterine growth restriction uteroplacental insufficiency epigenetic mechanisms long non-coding RNA DNA methylation |
| title | Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA |
| title_full | Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA |
| title_fullStr | Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA |
| title_full_unstemmed | Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA |
| title_short | Imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non-coding RNA |
| title_sort | imprinted gene alterations in the kidneys of growth restricted offspring may be mediated by a long non coding rna |
| topic | Intrauterine growth restriction uteroplacental insufficiency epigenetic mechanisms long non-coding RNA DNA methylation |
| url | https://www.tandfonline.com/doi/10.1080/15592294.2023.2294516 |
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