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

Research Project

Project/Area Number 16K20191
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Obstetrics and gynecology
Research InstitutionYamaguchi 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
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Keywords子宮内膜 / 脱落膜化 / epigenetics / IGFBP-1 / ヒストンアセチル化 / ゲノム編集
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.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (3 results)

All 2018 2017

All Journal Article (1 results) (of which Int'l Joint Research: 1 results,  Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (2 results)

  • [Journal Article] The distal upstream region of insulin-like growth factor-binding protein-1 enhances its expression in endometrial stromal cells during decidualization2018

    • Author(s)
      Tamura I, Jozaki K, Sato S, Shirafuta Y, Shinagawa M, Maekawa R, Taketani T, Asada H, Tamura H, Sugino N.
    • Journal Title

      J Biol Chem

      Volume: 293 Issue: 14 Pages: 5270-5280

    • DOI

      10.1074/jbc.ra117.000234

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Genome-wide epigenome analysis and genome editing identified a novel enhancer region for IGF binding protein-1 (IGFBP-1) expression in human endometrial stromal cells undergoing decidualization2018

    • Author(s)
      Isao Tamura, Haruka Takagi, Yuichiro Shirafuta, Norihiro Sugino
    • Organizer
      Society for the Study of Reproduction 2018 annual meeting
    • Related Report
      2017 Annual Research Report
  • [Presentation] エピゲノムから見えてきた子宮内膜脱落膜化の分子メカニズム2017

    • Author(s)
      田村 功
    • Organizer
      第62回日本生殖医学会学術講演会
    • Related Report
      2017 Annual Research Report

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Published: 2016-04-21   Modified: 2019-03-29  

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