2022
Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states
RAYMOND MARIO, Barry, Olivia SACCO, Amel MAMERI, Martin STOJASPAL, William KARTSONIS et. al.Základní údaje
Originální název
Rap1 regulates TIP60 function during fate transition between two-cell-like and pluripotent states
Autoři
RAYMOND MARIO, Barry, Olivia SACCO, Amel MAMERI, Martin STOJASPAL (203 Česká republika, domácí), William KARTSONIS, Pooja SHAH, Pablo DE IOANNES, Ctirad HOFR (203 Česká republika, garant, domácí), Jacques CÔTÉ a Agnel SFEIR
Vydání
Genes & Development, Cold Spring Harbor Laboratory Press, 2022, 0890-9369
Další údaje
Jazyk
angličtina
Typ výsledku
Článek v odborném periodiku
Obor
10608 Biochemistry and molecular biology
Stát vydavatele
Spojené státy
Utajení
není předmětem státního či obchodního tajemství
Odkazy
Impakt faktor
Impact factor: 10.500
Kód RIV
RIV/00216224:14310/22:00125447
Organizační jednotka
Přírodovědecká fakulta
UT WoS
000821506300006
Klíčová slova anglicky
2C-like; EPC1; MERVL; RAP1; TIP60; ZSCAN4; telomere
Štítky
Příznaky
Mezinárodní význam, Recenzováno
Změněno: 6. 3. 2023 10:29, Mgr. Martin Stojaspal, Ph.D.
Anotace
V originále
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.
Návaznosti
GA19-18226S, projekt VaV |
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LTAUSA19024, projekt VaV |
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