Involvement of histone acetylation in ovarian steroid-induced decidualization of human endometrial stromal cells.
Histone acetyltransferases and histone deacetylases (HDACs) determine the acetylation status of histones, regulating gene transcription. Decidualization is the progestin-induced differentiation of estrogen-primed endometrial stromal cells (ESCs), which is crucial for implantation and maintenance of pregnancy. We here show that trichostatin A (TSA), a specific HDAC inhibitor, enhances the up-regulation of decidualization markers such as insulin-like growth factor binding protein-1 (IGFBP-1) and prolactin in a dose-dependent manner that is directed by 17beta-estradiol (E(2)) plus progesterone (P(4)) in cultured ESCs, but not glandular cells, both isolated from human endometrium. Morphological changes resembling decidual transformation were also augmented by co-addition of TSA. Acid urea triton gel analysis and immunoblot using acetylated histone type-specific antibodies demonstrated that treatment with E(2) plus P(4) significantly increased the levels of acetylated H3 and H4 whose increment was augmented by co-treatment with TSA. Chromatin immunoprecipitation assay revealed that treatment with E(2) plus P(4) increased the amount of proximal progesterone-responsive region of IGFBP-1 promoter associated with acetylated H4, which was dramatically enhanced by co-addition of TSA. Taken together, our results suggest that histone acetylation is deeply involved in differentiation of human ESCs and that TSA has a potential as an enhancer of decidualization through promotion of progesterone action.
Sakai
Nozomi
N
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Shinanomach 35, Shinjuku-ku, Tokyo 160-8582, Japan.
Maruyama
Tetsuo
T
Sakurai
Rei
R
Masuda
Hirotaka
H
Yamamoto
Yurie
Y
Shimizu
Aki
A
Kishi
Ikuko
I
Asada
Hironori
H
Yamagoe
Satoshi
S
Yoshimura
Yasunori
Y
D000107:Acetylation; D000123:Acetyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism; D002460:Cell Line; D003656:Decidua / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D051548:Histone Acetyltransferases; D056572:Histone Deacetylase Inhibitors; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology*; D011388:Prolactin / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017154:Stromal Cells / Q000166:cytology / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects
D004791:Enzyme Inhibitors; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006877:Hydroxamic Acids; D018970:Insulin-Like Growth Factor Binding Protein 1; D029701:Saccharomyces cerevisiae Proteins; C012589:trichostatin A; D011374:Progesterone; D004958:Estradiol; D011388:Prolactin; D000123:Acetyltransferases; D051548:Histone Acetyltransferases; D006655:Histone Deacetylases