Inhibition of PHLDA2 transcription by DNA methylation and YY1 in goat placenta.
Gene
; 739: 144512, 2020 May 20.
Article
em En
| MEDLINE
| ID: mdl-32112983
ABSTRACT
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.
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Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Cabras
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Proteínas Nucleares
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Regulação da Expressão Gênica
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Fator de Transcrição YY1
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Histona Desacetilase 1
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Histona Desacetilases
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Pregnancy
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article