title: Importance of C/EBPβ binding and histone acetylation status in the promoter regions for induction of IGFBP-1, PRL, and Mn-SOD by cAMP in human endometrial stromal cells.
abstract: Dynamic changes of gene expressions occur in human endometrial stromal cells (ESCs) during decidualization. CCAAT/enhancer-binding proteinβ (C/EBPβ) regulates the expression of a number of decidualization-related genes. In addition to transcription factors, it is important to know the role of epigenetic mechanisms, such as histone modifications in the regulation of decidualization-related genes. This study investigated the molecular and epigenetic mechanisms by which cAMP up-regulates the expression of IGF-binding protein-1 (IGFBP-1), prolactin (PRL), and manganese superoxide dismutase (Mn-SOD) in ESC. ESCs isolated from proliferative phase endometrium were incubated with cAMP to induce decidualization. IGFBP-1, PRL, and Mn-SOD mRNA expressions were determined by real-time RT-PCR. The C/EBPβ binding and histone modification status (acetylation of histone-H3 lysine-27 [H3K27ac]) in the promoter were examined by chromatin immunoprecipitation assay. Knockdowns of C/EBPβ were performed using the small interfering RNA method. cAMP induced mRNA expressions of IGFBP-1 and PRL accompanied by the increases in both C/EBPβ binding activities and H3K27ac levels in the promoters. The stimulatory effects of cAMP on mRNA levels and H3K27ac levels were completely abolished by C/EBPβ knockdown. cAMP increased Mn-SOD mRNA levels and C/EBPβ binding activities in the enhancer region. C/EBPβ knockdown inhibited Mn-SOD mRNA levels. The H3K27ac levels in the enhancer were high before cAMP stimulus but were not further increased by cAMP and were not inhibited by C/EBPβ knockdown. These results show that C/EBPβ regulates the expression of IGFBP-1 and PRL by altering the histone acetylation status of their promoters but differently regulates Mn-SOD gene expression in human ESC during decidualization.
authors.affiliation: Department of Obstetrics and Gynecology, Yamaguchi University Graduate School of Medicine, Ube 755-8505, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Tamura
authors.forename: Shun
authors.initials: S
authors.lastname: Sato
authors.forename: Maki
authors.initials: M
authors.lastname: Okada
authors.forename: Manabu
authors.initials: M
authors.lastname: Tanabe
authors.forename: Lifa
authors.initials: L
authors.lastname: Lee
authors.forename: Ryo
authors.initials: R
authors.lastname: Maekawa
authors.forename: Hiromi
authors.initials: H
authors.lastname: Asada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Yamagata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tamura
authors.forename: Norihiro
authors.initials: N
authors.lastname: Sugino
mesh_terms: D000107:Acetylation; D000328:Adult; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D003656:Decidua / Q000378:metabolism; D004717:Endometrium / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D006657:Histones / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000378:metabolism*; D008875:Middle Aged; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000378:metabolism; D017154:Stromal Cells / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism*
chemical_list: D022782:CCAAT-Enhancer-Binding Protein-beta; D006657:Histones; C032231:IGFBP1 protein, human; D018970:Insulin-Like Growth Factor Binding Protein 1; D034741:RNA, Small Interfering; D011388:Prolactin; D000242:Cyclic AMP; D013482:Superoxide Dismutase