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

First Author  Guallar D Year  2012
Journal  Nucleic Acids Res Volume  40
Issue  18 Pages  8993-9007
PubMed ID  22844087 Mgi Jnum  J:193790
Mgi Id  MGI:5469559 Doi  10.1093/nar/gks686
Citation  Guallar D, et al. (2012) Expression of endogenous retroviruses is negatively regulated by the pluripotency marker Rex1/Zfp42. Nucleic Acids Res 40(18):8993-9007
abstractText  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.
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