Inhibition of PHLDA2 transcription by DNA methylation and YY1 in goat placenta
| Autor: | Xiao Ma, Lufang Su, Ruihong Wang, Yongxiong Yu, Caode Jiang, Shitian Yu |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Placenta Histone Deacetylase 1 Biology Histone Deacetylases Andrology 03 medical and health sciences 0302 clinical medicine Western blot Pregnancy Transcription (biology) Genetics Transcriptional regulation medicine Animals Promoter Regions Genetic Gene YY1 Transcription Factor reproductive and urinary physiology medicine.diagnostic_test YY1 Goats Nuclear Proteins General Medicine DNA Methylation Pleckstrin homology domain 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation 030220 oncology & carcinogenesis DNA methylation CpG Islands Female |
| Zdroj: | Gene. 739:144512 |
| ISSN: | 0378-1119 |
| DOI: | 10.1016/j.gene.2020.144512 |
| Popis: | Pleckstrin homology-like domain family A member 2 (PHLDA2) is essential for placental development in mammals. This study was conducted to investigate transcriptional regulation of goat PHLDA2 in the placenta. Real-time PCR and Western blot analyses showed different expression of the PHLDA2 in goat placentas during gestation with highest expression at 30 and 45 days post coitus (P 0.05). Luciferase reporter assays demonstrated the highest promoter activity in the region of -1023/+20 (P 0.05). A CpG island was defined within -631/+379 region, where lower level of CpG-methylation was detected with bisulfite sequencing PCR in the placenta than that in the spleen and liver (P 0.05). Meanwhile, in vitro experiments showed that 5-AzaC enhanced the gene expression in a dose-dependent manner. Site-directed mutation in vitro demonstrated that transcription factor Ying-yang 1 (YY1) had an inhibitory effect on the PHLDA2 expression, and the inhibition was further confirmed with overexpression and siRNA constructs of YY1. ChIP and RE-ChIP analyses further identified the binding of YY1 to the PHLDA2 promoter by interaction with histone deacetylase 1 (HDAC1) and HDAC3. This study uncovers the negative regulation of the CpG-methylation and YY1 on goat PHLDA2 expression. YY1 prefers binding to CpG-methylation sequences, and inhibits goat PHLDA2 expression via recruiting HDAC1 and 3. |
| Databáze: | OpenAIRE |
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