Regulation of human trophoblast syncytialization by histone demethylase LSD1.
作者： Jessica Milano-Foster , Soma Ray , Pratik Home , Avishek Ganguly , Bhaswati Bhattacharya
关键词:
摘要: A successful pregnancy is critically dependent upon proper placental development and function. During human placentation, villous cytotrophoblast (CTB) progenitors differentiate to form syncytiotrophoblasts (SynTBs), which provide the exchange surface between mother fetus secrete hormones ensure progression of pregnancy. However, epigenetic mechanisms that regulate SynTB differentiation from CTB are incompletely understood. Here, we show lysine-specific demethylase 1 (LSD1; also known as KDM1A), a histone demethylase, essential this process. LSD1 expressed both in differentiated SynTBs first-trimester villi; accordingly, expression maintained throughout gestation. Impairment function trophoblast inhibits induction endogenous retrovirally encoded genes SYNCYTIN1/endogenous retrovirus group W member 1, envelope (ERVW1) SYNCYTIN2/endogenous FRD (ERVFRD1), encoding fusogenic proteins critical syncytialization. Loss impairs chorionic gonadotropin α (CGA) β (CGB) genes, encode subunits gonadotrophin (hCG), hormone modulate maternal physiology during Mechanistic analyses at ERVW1, CGA, CGB loci revealed regulatory axis induces demethylation repressive H3 lysine 9 dimethylation (H3K9Me2) interacts with transcription factor GATA2 promote RNA polymerase II (RNA-POL-II) recruitment activate gene transcription. Our study reveals novel LSD1–GATA2 axis, regulates
sci-hub.se 参考文章(109)
Jennifer Quinn, Tilo Kunath, Janet Rossant, Mouse trophoblast stem cells. Methods in molecular medicine. ,vol. 121, pp. 125- 148 ,(2006) , 10.1385/1-59259-983-4:123
JOHN C. FIDDES, KAREN TALMADGE, Structure, expression, and evolution of the genes for the human glycoprotein hormones. Recent Progress in Hormone Research. ,vol. 40, pp. 43- 78 ,(1984) , 10.1016/B978-0-12-571140-1.50006-2
Margaret G. Petroff, Teresa A. Phillips, Hakhyun Ka, Judith L. Pace, Joan S. Hunt, Isolation and culture of term human trophoblast cells Methods in molecular medicine. ,vol. 121, pp. 203- 217 ,(2006) , 10.1385/1-59259-983-4:201
I. A. Maksakova, D. L. Mager, D. Reiss, Keeping active endogenous retroviral-like elements in check: the epigenetic perspective. Cellular and Molecular Life Sciences. ,vol. 65, pp. 3329- 3347 ,(2008) , 10.1007/S00018-008-8494-3
Sha Mi, Xinhua Lee, Xiang-ping Li, Geertruida M. Veldman, Heather Finnerty, Lisa Racie, Edward LaVallie, Xiang-Yang Tang, Philippe Edouard, Steve Howes, James C. Keith, John M. McCoy, Syncytin is a captive retroviral envelope protein involved in human placental morphogenesis. Nature. ,vol. 403, pp. 785- 789 ,(2000) , 10.1038/35001608
P F Policastro, S Daniels-McQueen, G Carle, I Boime, A map of the hCG beta-LH beta gene cluster. Journal of Biological Chemistry. ,vol. 261, pp. 5907- 5916 ,(1986) , 10.1016/S0021-9258(17)38469-7
M Bo, I Boime, Identification of the transcriptionally active genes of the chorionic gonadotropin beta gene cluster in vivo. Journal of Biological Chemistry. ,vol. 267, pp. 3179- 3184 ,(1992) , 10.1016/S0021-9258(19)50712-8
Hee Park, Sung Shim, Dong Cha, Combined Screening for Early Detection of Pre-Eclampsia. International Journal of Molecular Sciences. ,vol. 16, pp. 17952- 17974 ,(2015) , 10.3390/IJMS160817952
Stephen J. Renaud, Damayanti Chakraborty, Clifford W. Mason, M. A. Karim Rumi, Jay L. Vivian, Michael J. Soares, OVO-like 1 regulates progenitor cell fate in human trophoblast development Proceedings of the National Academy of Sciences of the United States of America. ,vol. 112, ,(2015) , 10.1073/PNAS.1507397112
D J Steger, J H Hecht, P L Mellon, GATA-binding proteins regulate the human gonadotropin alpha-subunit gene in the placenta and pituitary gland. Molecular and Cellular Biology. ,vol. 14, pp. 5592- 5602 ,(1994) , 10.1128/MCB.14.8.5592