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定义小鼠着床前后 TFAP2C 为中心的转录因子网络。

Defining a TFAP2C-centered transcription factor network during murine peri-implantation.

机构信息

Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, School of Life Sciences and Technology, Tongji University, Shanghai 200092, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China.

Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of the Ministry of Education, Orthopaedic Department of Tongji Hospital, Tongji University, Shanghai 200065, China; Frontier Science Center for Stem Cell Research, Tongji University, Shanghai 200092, China; Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200072, China.

出版信息

Dev Cell. 2024 May 6;59(9):1146-1158.e6. doi: 10.1016/j.devcel.2024.03.015. Epub 2024 Apr 3.

Abstract

Transcription factors (TFs) play important roles in early embryonic development, but factors regulating TF action, relationships in signaling cascade, genome-wide localizations, and impacts on cell fate transitions during this process have not been clearly elucidated. In this study, we used uliCUT&RUN-seq to delineate a TFAP2C-centered regulatory network, showing that it involves promoter-enhancer interactions and regulates TEAD4 and KLF5 function to mediate cell polarization. Notably, we found that maternal retinoic acid metabolism regulates TFAP2C expression and function by inducing the active demethylation of SINEs, indicating that the RARG-TFAP2C-TEAD4/KLF5 axis connects the maternal-to-zygotic transition to polarization. Moreover, we found that both genomic imprinting and SNP-transferred genetic information can influence TF positioning to regulate parental gene expressions in a sophisticated manner. In summary, we propose a ternary model of TF regulation in murine embryonic development with TFAP2C as the core element and metabolic, epigenetic, and genetic information as nodes connecting the pathways.

摘要

转录因子 (TFs) 在早期胚胎发育中发挥重要作用,但调控 TF 活性的因素、信号级联中的关系、全基因组定位以及在这一过程中对细胞命运转变的影响尚不清楚。在这项研究中,我们使用 uliCUT&RUN-seq 描绘了一个以 TFAP2C 为中心的调控网络,表明它涉及启动子-增强子相互作用,并调节 TEAD4 和 KLF5 的功能来介导细胞极化。值得注意的是,我们发现母体视黄酸代谢通过诱导 SINEs 的活性去甲基化来调节 TFAP2C 的表达和功能,表明 RARG-TFAP2C-TEAD4/KLF5 轴将母体到合子的转变与极化联系起来。此外,我们发现基因组印迹和 SNP 转移的遗传信息都可以以复杂的方式影响 TF 的定位,从而调节亲本基因的表达。总之,我们提出了一个以 TFAP2C 为核心元素的哺乳动物胚胎发育中 TF 调控的三元模型,代谢、表观遗传和遗传信息作为连接通路的节点。

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