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

Logo poskytovatele
Logo poskytovatele

Varování

Publikace nespadá pod Pedagogickou fakultu, ale pod Přírodovědeckou fakultu. Oficiální stránka publikace je na webu muni.cz.
Autoři

RAYMOND MARIO Barry SACCO Olivia MAMERI Amel STOJASPAL Martin KARTSONIS William SHAH Pooja DE IOANNES Pablo HOFR Ctirad CÔTÉ Jacques SFEIR Agnel

Rok publikování 2022
Druh Článek v odborném periodiku
Časopis / Zdroj Genes & Development
Fakulta / Pracoviště MU

Přírodovědecká fakulta

Citace
www http://genesdev.cshlp.org/content/early/2022/02/23/gad.349039.121.long
Doi http://dx.doi.org/10.1101/gad.349039.121
Klíčová slova 2C-like; EPC1; MERVL; RAP1; TIP60; ZSCAN4; telomere
Popis 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.
Související projekty:

Používáte starou verzi internetového prohlížeče. Doporučujeme aktualizovat Váš prohlížeč na nejnovější verzi.