Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42

Guallar, D. ; Pérez-Palacios, R. ; Climent, M. (Universidad de Zaragoza) ; Martínez-Abadía, I. ; Larraga, A. ; Fernández-Juan, M. ; Vallejo, C. ; Muniesa, P. (Universidad de Zaragoza) ; Schoorlemmer, J.

Resumen: Rex1/Zfp42 is a Yy1 -related zinc-finger protein whose expression is frequently used to identify pluripotent stem cells. We show that depletion of Rex1 levels notably affected self-renewal of mouse embryonic stem (ES) cells in clonal assays, in the absence of evident differences in expression of marker genes for pluripotency or differentiation. By contrast, marked differences in expression of several endogenous retroviral elements (ERVs) were evident upon Rex1 depletion. We demonstrate association of REX1 to specific elements in chromatin-immunoprecipitation assays, most strongly to muERV-L and to a lower extent to IAP and musD elements. Rex1 regulates muERV-L expression in vivo , as we show altered levels upon transient gain-and-loss of Rex1 function in pre-implantation embryos. We also find REX1 can associate with the lysine-demethylase LSD1/KDM1A, suggesting they act in concert. Similar to REX1 binding to retrotransposable elements (REs) in ES cells, we also detected binding of the REX1 related proteins YY1 and YY2 to REs, although the binding preferences of the two proteins were slightly different. Altogether, we show that Rex1 regulates ERV expression in mouse ES cells and during pre-implantation development and suggest that Rex1 and its relatives have evolved as regulators of endogenous retroviral transcription.

Idioma: Inglés

DOI: 10.1093/nar/gks686

Año: 2012

Publicado en: Nucleic Acids Research 40, 18 (2012), 8993-9007
ISSN: 0305-1048

Factor impacto JCR: 8.278 (2012)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 27 / 288 = 0.094 (2012) - Q1 - T1

Financiación: info:eu-repo/grantAgreement/ES/DGA-FEDER/B77
Financiación: info:eu-repo/grantAgreement/ES/DGA/PI110-09
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI07119
Financiación: info:eu-repo/grantAgreement/ES/IACS/PIPAMER-10-03
Financiación: info:eu-repo/grantAgreement/ES/MEC/BFU2004-00467

Tipo y forma: Article (Published version)

Área (Departamento): Área Anatom.Anatom.Patológ.Com (Dpto. Anatom.,Embri.Genét.Ani.)