A LINE1-Nucleolin Partnership Regulates Early Development and ESC Identity
Michelle Percharde, Chih-Jen Lin, Yafei Yin, Juan Guan, Gabriel A. Peixoto, Aydan Bulut-Karslioglu 6, Steffen Biechele, Bo Huang, Xiaohua Shen, Miguel Ramalho-Santos 7, 8
6 Present address: Max Planck Institute for Molecular Genetics, Berlin, Germany
7 Present address: Lunenfeld-Tanenbaum Research Institute and Department of Molecular Genetics, University of Toronto, Toronto, ON M5T 3H7, Canada
8 Lead Contact
Publication stage: In Press Corrected Proof
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Article Info
Publication History
Published: June 21, 2018 Accepted: May 17, 2018
Received in revised form: March 20, 2018 Received: August 12, 2017
In these two two-cell mouse embryos, the surface of the embryos is outlined in orange, the DNA in the nucleus is indicated in blue and the activity of the LINE-1 gene is indicated via bright red spots.
Ramalho-Santos lab/UCSF - Source/Fonte
Highlights
• LINE1 RNA is abundant and nuclear in mouse ESCs and pre-implantation embryos
• LINE1 knockdown inhibits ESC self-renewal and induces transition to a 2C state
• LINE1 RNA recruits Nucleolin/Kap1 to repress Dux and activate rRNA synthesis
• In embryos, LINE1 inhibition causes persistence of the 2C program and impairs ZGA
Summary
Transposable elements represent nearly half of mammalian genomes and are generally described as parasites, or “junk DNA.” The LINE1 retrotransposon is the most abundant class and is thought to be deleterious for cells, yet it is paradoxically highly expressed during early development. Here, we report that LINE1 plays essential roles in mouse embryonic stem cells (ESCs) and pre-implantation embryos. In ESCs, LINE1 acts as a nuclear RNA scaffold that recruits Nucleolin and Kap1/Trim28 to repress Dux, the master activator of a transcriptional program specific to the 2-cell embryo. In parallel, LINE1 RNA mediates binding of Nucleolin and Kap1 to rDNA, promoting rRNA synthesis and ESC self-renewal. In embryos, LINE1 RNA is required for Dux silencing, synthesis of rRNA, and exit from the 2-cell stage. The results reveal an essential partnership between LINE1 RNA, Nucleolin, Kap1, and peri-nucleolar chromatin in the regulation of transcription, developmental potency, and ESC self-renewal.
Keywords:
LINE1, retrotransposons, Nucleolin, Kap1, Dux, MERVL, hypertranscription, rRNA, 2-cell stage, ESCs
Source/Fonte: Cell
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