title: Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42.
abstract: 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.
authors: Regenerative Medicine Programme, IIS Aragón, Instituto Aragonés de Ciencias de Salud, Zaragoza, Avda. Gómez Laguna, 50009 Zaragoza, Spain.
authors: D
authors: D
authors: Guallar
authors: R
authors: R
authors: Pérez-Palacios
authors: M
authors: M
authors: Climent
authors: I
authors: I
authors: Martínez-Abadía
authors: A
authors: A
authors: Larraga
authors: M
authors: M
authors: Fernández-Juan
authors: C
authors: C
authors: Vallejo
authors: P
authors: P
authors: Muniesa
authors: J
authors: J
authors: Schoorlemmer
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D004622:Embryo, Mammalian / Q000378:metabolism; D053595:Embryonic Stem Cells / Q000166:cytology / Q000378:metabolism*; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation; D056466:Histone Demethylases; D051379:Mice; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D018626:Retroelements; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D050986:YY1 Transcription Factor / Q000378:metabolism
chemical_list: D015415:Biomarkers; D012333:RNA, Messenger; D018626:Retroelements; C513672:Zfp42 protein, mouse; D014157:Transcription Factors; D050986:YY1 Transcription Factor; C509847:YY2 protein, mouse; C494699:Yy1 protein, mouse; D056466:Histone Demethylases; C504076:KDM1a protein, mouse; D010089:Oxidoreductases, N-Demethylating