Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states Journal Article
| Authors: | Barry, R. M.; Sacco, O.; Mameri, A.; Stojaspal, M.; Kartsonis, W.; Shah, P.; De Ioannes, P.; Hofr, C.; Côté, J.; Sfeir, A. |
| Article Title: | Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states |
| Abstract: | 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 upregulation 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. |
| Keywords: | telomere; tip60; rap1; 2c-like; epc1; mervl; zscan4 |
| Journal Title: | Genes and Development |
| Volume: | 36 |
| Issue: | 5-6 |
| ISSN: | 0890-9369 |
| Publisher: | Cold Spring Harbor Laboratory Press |
| Date Published: | 2022-03-01 |
| Start Page: | 313 |
| End Page: | 330 |
| Language: | English |
| DOI: | 10.1101/gad.349039.121 |
| PUBMED: | 35210222 |
| PROVIDER: | scopus |
| PMCID: | PMC8973845 |
| DOI/URL: | |
| Notes: | Article -- Export Date: 2 May 2022 -- Source: Scopus |
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