Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta
During pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RN...
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MDPI AG
2020-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/21/8317 |
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| author | Rebekah R. Starks Rabab Abu Alhasan Haninder Kaur Kathleen A. Pennington Laura C. Schulz Geetu Tuteja |
| author_facet | Rebekah R. Starks Rabab Abu Alhasan Haninder Kaur Kathleen A. Pennington Laura C. Schulz Geetu Tuteja |
| author_sort | Rebekah R. Starks |
| collection | DOAJ |
| description | During pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RNA-seq data and ChIP-seq data for the enhancer associated mark, H3k27ac, to study gene regulation in the mouse placenta at embryonic day (e) 9.5, when the placenta is developing a complex network of blood vessels. We identified several upregulated transcription factors with enriched binding sites in e9.5-specific enhancers. The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. We then performed several experiments using mouse placenta and a human trophoblast cell line to understand the role of PLAGL1 in placental development. In the mouse placenta, <i>Plagl1</i> is expressed in endothelial cells of the labyrinth layer and is differentially expressed in placentas from mice with gestational diabetes compared to placentas from control mice in a sex-specific manner. In human trophoblast cells, siRNA knockdown significantly decreased expression of genes associated with placental vasculature development terms. In a tube assay, decreased <i>PLAGL1</i> expression led to reduced cord formation. These results suggest that <i>Plagl1</i> regulates overlapping gene networks in placental trophoblast and endothelial cells, and may play a critical role in placental development in normal and complicated pregnancies. |
| first_indexed | 2024-03-10T15:03:55Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:03:55Z |
| publishDate | 2020-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-4a158dfc26fa4013b21540b4a2a17c592023-11-20T19:57:48ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-11-012121831710.3390/ijms21218317Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the PlacentaRebekah R. Starks0Rabab Abu Alhasan1Haninder Kaur2Kathleen A. Pennington3Laura C. Schulz4Geetu Tuteja5Genetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USAGenetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USAGenetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USAObstetrics and Gynecology, Baylor College of Medicine, Houston, TX 77030, USAObstetrics, Gynecology and Women’s Health, University of Missouri, Columba, MO 65212, USAGenetics, Development, and Cell Biology, Iowa State University, Ames, IA 50011, USADuring pregnancy, the placenta is important for transporting nutrients and waste between the maternal and fetal blood supply, secreting hormones, and serving as a protective barrier. To better understand placental development, we must understand how placental gene expression is regulated. We used RNA-seq data and ChIP-seq data for the enhancer associated mark, H3k27ac, to study gene regulation in the mouse placenta at embryonic day (e) 9.5, when the placenta is developing a complex network of blood vessels. We identified several upregulated transcription factors with enriched binding sites in e9.5-specific enhancers. The most enriched transcription factor, PLAGL1 had a predicted motif in 233 regions that were significantly associated with vasculature development and response to insulin stimulus genes. We then performed several experiments using mouse placenta and a human trophoblast cell line to understand the role of PLAGL1 in placental development. In the mouse placenta, <i>Plagl1</i> is expressed in endothelial cells of the labyrinth layer and is differentially expressed in placentas from mice with gestational diabetes compared to placentas from control mice in a sex-specific manner. In human trophoblast cells, siRNA knockdown significantly decreased expression of genes associated with placental vasculature development terms. In a tube assay, decreased <i>PLAGL1</i> expression led to reduced cord formation. These results suggest that <i>Plagl1</i> regulates overlapping gene networks in placental trophoblast and endothelial cells, and may play a critical role in placental development in normal and complicated pregnancies.https://www.mdpi.com/1422-0067/21/21/8317RNA-seqChIP-seqenhancerstranscription factorsplacentaPLAGL1 |
| spellingShingle | Rebekah R. Starks Rabab Abu Alhasan Haninder Kaur Kathleen A. Pennington Laura C. Schulz Geetu Tuteja Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta International Journal of Molecular Sciences RNA-seq ChIP-seq enhancers transcription factors placenta PLAGL1 |
| title | Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta |
| title_full | Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta |
| title_fullStr | Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta |
| title_full_unstemmed | Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta |
| title_short | Transcription Factor PLAGL1 Is Associated with Angiogenic Gene Expression in the Placenta |
| title_sort | transcription factor plagl1 is associated with angiogenic gene expression in the placenta |
| topic | RNA-seq ChIP-seq enhancers transcription factors placenta PLAGL1 |
| url | https://www.mdpi.com/1422-0067/21/21/8317 |
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