Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states.

Autor:	Barry RM; Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.; Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA., Sacco O; Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA., Mameri A; St-Patrick Research Group in Basic Oncology; CHU de Québec-Université Laval Research Center-Oncology Division, Laval University Cancer Research Center, Quebec City, Quebec G1R 3S3, Canada., Stojaspal M; Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA.; LifeB, Functional Genomics and Proteomics, National Centre for Biomolecular Research, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic., Kartsonis W; Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA., Shah P; Skirball Institute of Biomolecular Medicine, Department of Cell Biology, New York University School of Medicine, New York, New York 10016, USA., De Ioannes P; Skirball Institute of Biomolecular Medicine, Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA., Hofr C; LifeB, Functional Genomics and Proteomics, National Centre for Biomolecular Research, Faculty of Science, Masaryk University, 625 00 Brno, Czech Republic.; Institute of Biophysics of the Czech Academy of Sciences, Scientific Incubator, 612 65 Brno, Czech Republic., Côté J; St-Patrick Research Group in Basic Oncology; CHU de Québec-Université Laval Research Center-Oncology Division, Laval University Cancer Research Center, Quebec City, Quebec G1R 3S3, Canada., Sfeir A; Molecular Biology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, New York 10065, USA.
Jazyk:	angličtina
Zdroj:	Genes & development [Genes Dev] 2022 Mar 01; Vol. 36 (5-6), pp. 313-330. Date of Electronic Publication: 2022 Feb 24.
DOI:	10.1101/gad.349039.121
Abstrakt:	In mammals, the conserved telomere binding protein Rap1 serves a diverse set of nontelomeric functions, including activation of the NF-kB signaling pathway, maintenance of metabolic function in vivo, and transcriptional regulation. Here, we uncover the mechanism by which Rap1 modulates gene expression. Using a separation-of-function allele, we show that Rap1 transcriptional regulation is largely independent of TRF2-mediated binding to telomeres and does not involve direct binding to genomic loci. Instead, Rap1 interacts with the TIP60/p400 complex and modulates its histone acetyltransferase activity. Notably, we show that deletion of Rap1 in mouse embryonic stem cells increases the fraction of two-cell-like cells. Specifically, Rap1 enhances the repressive activity of Tip60/p400 across a subset of two-cell-stage genes, including Zscan4 and the endogenous retrovirus MERVL. Preferential up-regulation of genes proximal to MERVL elements in Rap1-deficient settings implicates these endogenous retroviral elements in the derepression of proximal genes. Altogether, our study reveals an unprecedented link between Rap1 and the TIP60/p400 complex in the regulation of pluripotency. (© 2022 Barry et al.; Published by Cold Spring Harbor Laboratory Press.)
Databáze:	MEDLINE
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