Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy loss.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 30100398.
- Also identified by DOI 10.1016/j.ebiom.2018.07.042 and PMC identifier 6154871.
- Licence recorded as CC BY-NC-ND.
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Abstract
Aberrant DNA methylation is considered to be a potential cause of recurrent pregnancy loss (RPL), while potential mechanism has not yet been elucidated. In order to uncover the contribution of the perturbation of DNA methylation in RPL, we performed genome-wide DNA methylation analysis combined with genome-wide gene expression in decidua tissue. Totally, 539 differentially methylated regions (DMRs) were identified and significantly correlated with gene expressions. We observed that hypo-methylated DMR near CREB5 recruited transcription factors binding, such as P53 and SP1, and in turn upregulated CREB5. Compromised cell migration and apoptosis were observed in human CREB5 overexpression trophoblast cell lines, indicating dysfunctional trophoblast cells might contribute to RPL after hypo-methylation of CREB5. In addition, overexpression of CREB5 altered cell cycle. Our data highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a potential diagnostic biomarker for RPL.
Medical subject headings
- Abortion, Habitual
- Cyclic AMP Response Element-Binding Protein A
- DNA Methylation
- Genetic Predisposition to Disease
- Transcriptome