Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy lossResearch in context

Mingming Yu; Guizhen Du; Qiaoqiao Xu; Zhenyao Huang; Xiaomin Huang; Yufeng Qin; Li Han; Yun Fan; Yan Zhang; Xiumei Han; Ziyan Jiang; Yankai Xia; Xinru Wang; Chuncheng Lu

EBioMedicine (Sep 2018)

Integrated analysis of DNA methylome and transcriptome identified CREB5 as a novel risk gene contributing to recurrent pregnancy lossResearch in context

Mingming Yu,
Guizhen Du,
Qiaoqiao Xu,
Zhenyao Huang,
Xiaomin Huang,
Yufeng Qin,
Li Han,
Yun Fan,
Yan Zhang,
Xiumei Han,
Ziyan Jiang,
Yankai Xia,
Xinru Wang,
Chuncheng Lu

Affiliations

Mingming Yu: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Guizhen Du: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Qiaoqiao Xu: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Zhenyao Huang: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Xiaomin Huang: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Yufeng Qin: Epigenetics & Stem Cell Biology Laboratory, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA
Li Han: Department of Obstetrics, Huai-An First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China
Yun Fan: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Yan Zhang: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Xiumei Han: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Ziyan Jiang: Department of Obstetrics and Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210000, China
Yankai Xia: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Xinru Wang: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China
Chuncheng Lu: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China; Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 210029, China; Corresponding author at: State Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing 210029, China.

Journal volume & issue: Vol. 35
pp. 334 – 344

Abstract

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Background: Aberrant DNA methylation is considered to be a potential cause of recurrent pregnancy loss (RPL), while potential mechanism has not yet been elucidated. Methods: 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. Findings: 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. Interpretation: Our data highlights a role of CREB5 involved in the pathogenesis of RPL, and CREB5 maybe a potential diagnostic biomarker for RPL. Keywords: Recurrent pregnancy loss, DNA methylation, Gene expression, CREB5

Published in EBioMedicine

ISSN: 2352-3964 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Medicine (General)
Website: http://www.journals.elsevier.com/ebiomedicine/

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