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 | Zendy

Isao Tamura | Zendy; Shun Sato | Zendy; Maki Okada | Zendy; Manabu Tanabe | Zendy; Lifa Lee | Zendy; Ryo Maekawa | Zendy; Hiromi Asada | Zendy; Yoshiaki Yamagata | Zendy; Hiroshi Tamura | Zendy; Norihiro Sugino | Zendy

Open Access

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

Author(s) -

Isao Tamura,

Shun Sato,

Maki Okada,

Manabu Tanabe,

Lifa Lee,

Ryo Maekawa,

Hiromi Asada,

Yoshiaki Yamagata,

Hiroshi Tamura,

Norihiro Sugino

Publication year - 2013

Publication title -

endocrinology

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 1.674

H-Index - 257

eISSN - 1945-7170

pISSN - 0013-7227

DOI - 10.1210/en.2013-1569

Subject(s) - decidualization , gene knockdown , chromatin immunoprecipitation , ccaat enhancer binding proteins , histone , biology , microbiology and biotechnology , stromal cell , regulation of gene expression , h3k4me3 , epigenetics , transcription factor , endocrinology , promoter , gene expression , chemistry , medicine , cancer research , gene , nuclear protein , biochemistry

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.

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