The distal upstream region of insulin-like growth factor binding protein-1 enhances its expression in endometrial stromal cells during decidualization

2017 Fiscal Year Final Research Report

• Project/Area Number: 16K20191
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: TAMURA Isao 山口大学, 医学部附属病院, 助教 (40610663)
• Project Period (FY): 2016-04-01 – 2018-03-31
• Keywords: 子宮内膜 / 脱落膜化 / epigenetics

Outline of Final Research Achievements

IGFBP-1 is a specific decidualization marker and has increased H3K27ac levels in its distal upstream region. Here, using a luciferase reporter gene construct containing this IGFBP-1 upstream region, we tested the hypothesis that it is an IGFBP-1 enhancer. To induce decidualization, we incubated ESCs with cAMP and found that cAMP increased luciferase expression, indicating that decidualization increased the transcriptional activity from the IGFBP-1 upstream region. Furthermore, CRISPR/Cas9-mediated deletion of this region significantly reduced IGFBP-1 expression, confirming its role as an IGFBP-1 enhancer. A ChIP assay revealed that cAMP increased the recruitment of the transcriptional regulators C/EBPβand FOXO1 to the IGFBP-1 enhancer in ESCs. These results indicate that the region -4701 to -7501 bp upstream of IGFBP-1 functions as an enhancer for IGFBP-1 expression in ESCs undergoing decidualization.

Free Research Field

生殖内分泌学