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@article{1837781, author = {Raymond Mario, Barry and Sacco, Olivia and Mameri, Amel and Stojaspal, Martin and Kartsonis, William and Shah, Pooja and De Ioannes, Pablo and Hofr, Ctirad and Côté, Jacques and Sfeir, Agnel}, article_number = {5-6}, doi = {http://dx.doi.org/10.1101/gad.349039.121}, keywords = {2C-like; EPC1; MERVL; RAP1; TIP60; ZSCAN4; telomere}, language = {eng}, issn = {0890-9369}, journal = {Genes & Development}, title = {Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states}, url = {http://genesdev.cshlp.org/content/early/2022/02/23/gad.349039.121.long}, volume = {36}, year = {2022} }
TY - JOUR ID - 1837781 AU - Raymond Mario, Barry - Sacco, Olivia - Mameri, Amel - Stojaspal, Martin - Kartsonis, William - Shah, Pooja - De Ioannes, Pablo - Hofr, Ctirad - Côté, Jacques - Sfeir, Agnel PY - 2022 TI - Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states JF - Genes & Development VL - 36 IS - 5-6 SP - 313-330 EP - 313-330 PB - Cold Spring Harbor Laboratory Press SN - 08909369 KW - 2C-like KW - EPC1 KW - MERVL KW - RAP1 KW - TIP60 KW - ZSCAN4 KW - telomere UR - http://genesdev.cshlp.org/content/early/2022/02/23/gad.349039.121.long N2 - 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. ER -
RAYMOND MARIO, Barry, Olivia SACCO, Amel MAMERI, Martin STOJASPAL, William KARTSONIS, Pooja SHAH, Pablo DE IOANNES, Ctirad HOFR, Jacques CÔTÉ a Agnel SFEIR. Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states. \textit{Genes \&{} Development}. Cold Spring Harbor Laboratory Press, roč.~36, 5-6, s.~313-330. ISSN~0890-9369. doi:10.1101/gad.349039.121. 2022.
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