Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs
Abstract PDX1 is a crucial transcription factor in pancreas development and mature β-cell function. However, the regulation of PDX1 expression in larger animals mirroring human pancreas morphogenesis and endocrine maturation remains poorly understood. Therefore, we conducted a comparative analysis t...
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Nature Portfolio
2024-11-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-024-77614-0 |
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| author | Naeimeh Rezaei Kianoush Dormiani Abbas Kiani-Esfahani Somayeh Mirdamadian Mohsen Rahmani Farnoosh Jafarpour Mohammad Hossein Nasr-Esfahani |
| author_facet | Naeimeh Rezaei Kianoush Dormiani Abbas Kiani-Esfahani Somayeh Mirdamadian Mohsen Rahmani Farnoosh Jafarpour Mohammad Hossein Nasr-Esfahani |
| author_sort | Naeimeh Rezaei |
| collection | DOAJ |
| description | Abstract PDX1 is a crucial transcription factor in pancreas development and mature β-cell function. However, the regulation of PDX1 expression in larger animals mirroring human pancreas morphogenesis and endocrine maturation remains poorly understood. Therefore, we conducted a comparative analysis to characterize regulatory regions of goat PDX1 gene and assessed their transcriptional activity by transient transfection of several transgenic EGFP constructs in β- and non-β cell lines. We recognized several highly conserved regions encompassing the promoter and cis-regulatory elements (Area I-IV) at 5’ flanking sequence of the genes. Within the promoter, we identified that a key E-box and nearby CAAT element synergistically drive transcription, constituting the basal promoter of goat PDX1 gene. Furthermore, each recognized regulatory area separately enhances this basal promoter activity in β-cells compared to non-β cells; however, cooperatively, they exhibit a bifunctional regulatory effect on transcription. Additionally, the intact ~ 3 kb upstream region (Area I-III) functions as the most efficient reporter transgene in vitro and shows islet-specific expression in native rat pancreas. Together, our findings suggest that the regulation of goat PDX1 gene is governed by conserved regions similar to other mammals, while both structurally and functionally, these regions exhibit a closer resemblance to those found in humans. |
| format | Article |
| id | doaj-art-f25a74f0e1bc4f98b22f5064fe1b5d33 |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Nature Portfolio |
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| series | Scientific Reports |
| spelling | doaj-art-f25a74f0e1bc4f98b22f5064fe1b5d332024-11-10T12:21:04ZengNature PortfolioScientific Reports2045-23222024-11-0114111310.1038/s41598-024-77614-0Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologsNaeimeh Rezaei0Kianoush Dormiani1Abbas Kiani-Esfahani2Somayeh Mirdamadian3Mohsen Rahmani4Farnoosh Jafarpour5Mohammad Hossein Nasr-Esfahani6Department of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECRDepartment of Animal Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECRAbstract PDX1 is a crucial transcription factor in pancreas development and mature β-cell function. However, the regulation of PDX1 expression in larger animals mirroring human pancreas morphogenesis and endocrine maturation remains poorly understood. Therefore, we conducted a comparative analysis to characterize regulatory regions of goat PDX1 gene and assessed their transcriptional activity by transient transfection of several transgenic EGFP constructs in β- and non-β cell lines. We recognized several highly conserved regions encompassing the promoter and cis-regulatory elements (Area I-IV) at 5’ flanking sequence of the genes. Within the promoter, we identified that a key E-box and nearby CAAT element synergistically drive transcription, constituting the basal promoter of goat PDX1 gene. Furthermore, each recognized regulatory area separately enhances this basal promoter activity in β-cells compared to non-β cells; however, cooperatively, they exhibit a bifunctional regulatory effect on transcription. Additionally, the intact ~ 3 kb upstream region (Area I-III) functions as the most efficient reporter transgene in vitro and shows islet-specific expression in native rat pancreas. Together, our findings suggest that the regulation of goat PDX1 gene is governed by conserved regions similar to other mammals, while both structurally and functionally, these regions exhibit a closer resemblance to those found in humans.https://doi.org/10.1038/s41598-024-77614-0Pancreas developmentIslet beta cell (β-cell)PDX1Tissue‐specific transcription factorDiabetesCis-Regulatory elements |
| spellingShingle | Naeimeh Rezaei Kianoush Dormiani Abbas Kiani-Esfahani Somayeh Mirdamadian Mohsen Rahmani Farnoosh Jafarpour Mohammad Hossein Nasr-Esfahani Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs Scientific Reports Pancreas development Islet beta cell (β-cell) PDX1 Tissue‐specific transcription factor Diabetes Cis-Regulatory elements |
| title | Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs |
| title_full | Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs |
| title_fullStr | Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs |
| title_full_unstemmed | Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs |
| title_short | Characterization and functional evaluation of goat PDX1 regulatory modules through comparative analysis of conserved interspecies homologs |
| title_sort | characterization and functional evaluation of goat pdx1 regulatory modules through comparative analysis of conserved interspecies homologs |
| topic | Pancreas development Islet beta cell (β-cell) PDX1 Tissue‐specific transcription factor Diabetes Cis-Regulatory elements |
| url | https://doi.org/10.1038/s41598-024-77614-0 |
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