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

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F22%3A00559188" target="_blank" >RIV/68081707:_____/22:00559188 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216224:14310/22:00125447

Výsledek na webu

<a href="http://genesdev.cshlp.org/content/36/5-6/313" target="_blank" >http://genesdev.cshlp.org/content/36/5-6/313</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1101/gad.349039.121" target="_blank" >10.1101/gad.349039.121</a>

Jazyk výsledku

angličtina

Název v původním jazyce

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

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

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

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10601 - Cell biology

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2022

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Genes and Development

ISSN

0890-9369

e-ISSN

1549-5477

Svazek periodika

36

Číslo periodika v rámci svazku

5-6

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

18

Strana od-do

313-330

Kód UT WoS článku

000821506300006

EID výsledku v databázi Scopus

2-s2.0-85127841683