1. Academic Validation
  2. Defining a TFAP2C-centered transcription factor network during murine peri-implantation

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

  • Dev Cell. 2024 May 6;59(9):1146-1158.e6. doi: 10.1016/j.devcel.2024.03.015.
Rui Gao 1 Guang Yang 2 Mengting Wang 3 Jing Xiao 4 Shanru Yi 3 Yanxin Huang 3 Zhenxiang Guo 3 Yunzhe Kang 3 Qianzheng Fu 3 Mingzhu Wang 3 Ben Xu 3 Shijun Shen 5 Qianshu Zhu 5 Meng Liu 5 Liping Wang 5 Xinyu Cui 5 Shanshan Yi 5 Xiaochen Kou 3 Yanhong Zhao 3 Liang Gu 5 Hong Wang 3 Shaorong Gao 6 Cizhong Jiang 7 Jiayu Chen 8
Affiliations

Affiliations

  • 1 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. Electronic address: [email protected].
  • 2 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.
  • 3 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.
  • 4 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; 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.
  • 5 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.
  • 6 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; Shanghai Institute of Stem Cell Research and Clinical Translation, Shanghai East Hospital, Tongji University, Shanghai 200120, China. Electronic address: [email protected].
  • 7 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. Electronic address: [email protected].
  • 8 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. Electronic address: [email protected].
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.

Keywords

TFAP2C; embryo development; epigenetic; imprinting; metabolism; polarization; promoter-enhancer interaction; retinoic acid; single nucleotide polymorphism; transcription factor.

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