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Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states
RM. Barry, O. Sacco, A. Mameri, M. Stojaspal, W. Kartsonis, P. Shah, P. De Ioannes, C. Hofr, J. Côté, A. Sfeir
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
Grantová podpora
F30 DK118901
NIDDK NIH HHS - United States
P30 CA008748
NCI NIH HHS - United States
R01 DK102562
NIDDK NIH HHS - United States
NLK
Free Medical Journals
od 1987 do Před 6 měsíci
Freely Accessible Science Journals
od 1987-03-01 do Před 6 měsíci
PubMed Central
od 1997 do Před 6 měsíci
Europe PubMed Central
od 1997 do Před 6 měsíci
Open Access Digital Library
od 1987-01-01
Open Access Digital Library
od 1987-03-01
PubMed
35210222
DOI
10.1101/gad.349039.121
Knihovny.cz E-zdroje
- MeSH
- genom MeSH
- myší embryonální kmenové buňky metabolismus MeSH
- myši MeSH
- proteiny vázající telomery * genetika metabolismus MeSH
- regulace genové exprese MeSH
- savci genetika MeSH
- telomery * metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
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.
Citace poskytuje Crossref.org
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