Hypomethylation of PRDM1 is associated with recurrent pregnancy loss.
Abortion, Habitual
/ genetics
Apoptosis
/ genetics
Case-Control Studies
Cell Cycle
/ genetics
Cell Movement
/ genetics
DNA Methylation
/ genetics
Female
GATA2 Transcription Factor
/ metabolism
Gene Expression Regulation
Hepatocyte Nuclear Factor 3-alpha
/ metabolism
Humans
Positive Regulatory Domain I-Binding Factor 1
/ genetics
Pregnancy
Trophoblasts
/ metabolism
PRDM1
DNA methylation
gene expression
recurrent pregnancy loss
villus
Journal
Journal of cellular and molecular medicine
ISSN: 1582-4934
Titre abrégé: J Cell Mol Med
Pays: England
ID NLM: 101083777
Informations de publication
Date de publication:
06 2020
06 2020
Historique:
received:
21
03
2019
revised:
21
11
2019
accepted:
09
12
2019
pubmed:
30
4
2020
medline:
30
4
2021
entrez:
30
4
2020
Statut:
ppublish
Résumé
Recurrent pregnancy loss (RPL) rates have continued to rise during the last few decades, yet the underlying mechanisms remain poorly understood. An emerging area of interest is the mediation of gene expression by DNA methylation during early pregnancy. Here, genome-wide DNA methylation from placental villi was profiled in both RPL patients and controls. Subsequently, differentially expressed genes were analysed for changes in gene expression. Many significant differentially methylated regions (DMRs) were identified near genes dysregulated in RPL including PRDM1. Differentially expressed genes were enriched in immune response pathways indicating that abnormal immune regulation contributes to RPL. Integrated analysis of DNA methylome and transcriptome demonstrated that the expression level of PRDM1 is fine-tuned by DNA methylation. Specifically, hypomethylation near the transcription start site of PRDM1 can recruit other transcription factors, like FOXA1 and GATA2, leading to up-regulation of gene expression and resulting in changes to trophoblast cell apoptosis and migration. These phenotypic differences may be involved in RPL. Overall, our study provides new insights into PRDM1-dependent regulatory effects during RPL and suggests both a mechanistic link between changes in PRDM1 expression, as well as a role for PRDM1 methylation as a potential biomarker for RPL diagnosis.
Identifiants
pubmed: 32349189
doi: 10.1111/jcmm.15335
pmc: PMC7299696
doi:
Substances chimiques
FOXA1 protein, human
0
GATA2 Transcription Factor
0
Hepatocyte Nuclear Factor 3-alpha
0
PRDM1 protein, human
138415-26-6
Positive Regulatory Domain I-Binding Factor 1
EC 2.1.1.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
7072-7077Informations de copyright
© 2020 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.
Références
Am J Reprod Immunol. 2018 Apr;79(4):e12825
pubmed: 29430761
Development. 2017 Mar 1;144(5):876-888
pubmed: 28232602
Hum Reprod. 2002 Jun;17(6):1649-56
pubmed: 12042293
Bioinformatics. 2002 Feb;18(2):333-4
pubmed: 11847087
Int J Epidemiol. 2012 Apr;41(2):405-13
pubmed: 22253313
Nature. 2012 Sep 6;489(7414):75-82
pubmed: 22955617
Reprod Sci. 2018 Jan;25(1):131-139
pubmed: 28443481
Rev Obstet Gynecol. 2009 Spring;2(2):76-83
pubmed: 19609401
Nucleic Acids Res. 2003 Jul 1;31(13):3651-3
pubmed: 12824386
Placenta. 2017 Dec;60 Suppl 1:S61-S66
pubmed: 28526138
Hum Reprod. 2010 Jun;25(6):1411-4
pubmed: 20382970
Front Immunol. 2016 Nov 17;7:510
pubmed: 27909437
Nat Protoc. 2013 Dec;8(12):2502-15
pubmed: 24263090
Lancet. 1990 Sep 15;336(8716):673-5
pubmed: 1975862
Nature. 2005 Jul 14;436(7048):207-13
pubmed: 15937476
J Cell Mol Med. 2020 Jun;24(12):7072-7077
pubmed: 32349189
Cell Stem Cell. 2018 Jan 4;22(1):50-63.e6
pubmed: 29249463