Elucidation of the transcriptional network centered on the master gene activated by decidualization of human endometrial stromal cells

2019 Fiscal Year Final Research Report

• Project/Area Number: 17K11239
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Obstetrics and gynecology
• Research Institution: Yamaguchi University
• Principal Investigator: TAKETANI Toshiaki 山口大学, 医学部附属病院, 講師 (70464328)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Keywords: 脱落膜化 / 子宮内膜間質細胞 / 転写因子

Outline of Final Research Achievements

Human endometrial stromal cells (ESCs) undergo decidualization, which is crucial for embryo implantation and maintenance of pregnancy. We previously reported that a number of genes are up- or down-regulated during decidualization and that epigenetic changes (increase of H3K27ac) occur throughout the genome during decidualization of ESCs. In this study, we aimed to identify a master transcription regulator of decidualization, which is an up-stream transcription factor that regulates genome-wide gene expressions and epigenome status. Based on genome-wide expression data, we focused on C/EBPb as a candidate mater regulator. RNA-seq analysis with C/EBPb knockdown revealed that 53.4% of up- or downregulated genes by decidualization were under the regulation of C/EBPb. ChIP-seq analysis showed that C/EBPb regulates almost all the increase of H3K27ac (99.3 %) during decidualization. Taken together, our study showed that C/EBPb is one of master regulator for decidualization.

Free Research Field

生殖医学

Academic Significance and Societal Importance of the Research Achievements

転写因子C/EBPbの脱落膜化におけるマスター遺伝子としての重要性をゲノムワイドな視点から追及することができた。さらに、C/EBPbは脱落膜化における遺伝子発現のみならず、ヒストン修飾変化の多くも司っていることが分かった。脱落膜化におけるゲノムワイドエピゲノム変化については、我々が世界に先駆けて証明した事象であり、この制御機構を証明するに至ったことは非常に価値があると考えている。