title: A repressive role of enhancer of zeste homolog 2 in 11β-hydroxysteroid dehydrogenase type 2 expression in the human placenta.
abstract: The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 at the promoter of the 11β-HSD2 gene. Further studies revealed that, upon syncytialization, human chorionic gonadotropin reduced the phosphorylation of retinoblastoma protein (pRB) via activation of the cAMP/PKA pathway, which sequesters E2F transcription factor 1 (E2F1), the transcription factor for EZH2 expression. As a result of inactivation of the pRB-E2F1-EZH2 pathway, the repressive marker trimethylation of histone H3 lysine 27 at the 11β-HSD2 promoter is removed, which leads to the robust expression of 11β-HSD2 during syncytialization.
authors.affiliation: From the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.|the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China, and.
authors.forename: Rujuan
authors.initials: R
authors.lastname: Zuo
authors.affiliation: the Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200135, China.
authors.forename: Xiaohui
authors.initials: X
authors.lastname: Liu
authors.affiliation: From the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.|the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China, and.
authors.forename: Wangsheng
authors.initials: W
authors.lastname: Wang
authors.affiliation: From the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China.|the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China, and.
authors.forename: Wenjiao
authors.initials: W
authors.lastname: Li
authors.affiliation: the Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200135, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Ying
authors.affiliation: From the Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200135, China, sungangrenji@hotmail.com.|the Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Shanghai 200135, China, and.
authors.forename: Kang
authors.initials: K
authors.lastname: Sun
mesh_terms: D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2 / Q000096:biosynthesis* / Q000235:genetics; D000328:Adult; D000242:Cyclic AMP / Q000235:genetics / Q000378:metabolism; D050687:E2F1 Transcription Factor / Q000235:genetics / Q000378:metabolism; D000071221:Enhancer of Zeste Homolog 2 Protein / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008745:Methylation; D010920:Placenta / Q000201:enzymology*; D011247:Pregnancy; D011257:Pregnancy Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D015290:Second Messenger Systems / Q000502:physiology*
chemical_list: D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D006657:Histones; D011257:Pregnancy Proteins; D012097:Repressor Proteins; D016160:Retinoblastoma Protein; D000242:Cyclic AMP; D043209:11-beta-Hydroxysteroid Dehydrogenase Type 2; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein
keywords: 11β-hydroxysteroid dehydrogenase 2; E2F transcription factor; EZH2; fetal development; glucocorticoid; histone methylation; histone modification; placenta; trophoblast