体外受精（IVF）是当前最常用的辅助生殖技术，然而IVF的种植率仍有待提高。研究表明子宫内膜容受性差是胚胎种植失败的主要因素之一，其机制目前尚不清楚。我们前期通过ATAC-seq发现IVF反复种植失败与IVF妊娠患者其子宫内膜的染色质开放结构具有显著差异且富集转录因子FLI1。进一步预实验提示：FLI1通过激活增强子从而促进长非编码RNA-LINC00473的转录，而LINC00473与ERα的结合能显著减弱ERα在容受性相关基因（如PR）启动子上的结合及其转录。据此，我们提出本项目的研究假说：子宫内膜中异常开放的染色质促发FLI1结合在LINC00473基因的增强子上并激活其表达→LINC00473与ERα结合并阻碍ERα在容受性相关基因启动子上的结合→子宫内膜容受性相关基因转录下调→胚胎种植失败。本项目的探索将揭示调控子宫内膜容受性的全新分子机制，为IVF胚胎种植失败的防治提供新思路。

In vitro fertilization (IVF) is the most popular assisted reproductive technology. Nevertheless, the success rate of embryo implantation is yet to be improved. Currently, poor endometrial receptivity is regarded as the major factor for the failure of embryo implantation but its mechanism is poorly understood. In our preliminary study, we found that the chromatin structures displayed significant disparity in IVF recipients (repeated implantation failure (RIF) vs pregnancy). Bioinformatic analysis showed that the motif of transcription factor FLI1was significantly enriched in the differential chromatin regions between the two groups. Intriguingly, our preliminary data implied that FLI1 may increase LINC00473 expression through enhancer activation. Furthermore, we found that the LINC0043 interacted with ERα and reduced its binding of the promoter of the genes (e.g. PR) related to endometrial receptivity. Hence, we hypothesize that aberrant chromatin opening creates the binding site for transcription factor FLI1 which activate the transcription of LINC00473 via enhancer-promoter interaction; Upregulated LINC00473 interacts with ERα and disrupts the binding of ERα on the promoters of the genes related to endometrial receptivity, leading to transcriptional repression. We believe that this project will provide novel insights on the mechanisms of endometrial receptivity and the prevention and treatment of failure of embryo implantation in IVF.