Proviral Silencing in Embryonic Cells Is Regulated by Yin Yang 1

•Deletion of YY1-binding site from the MMLV LTR impairs rapid onset of silencing•In YY1 knockdown cells, silencing of endogenous and exogenous retroviruses is impaired•YY1 binding correlates with H3K9me3 histone marks, but not with H3K27me3 marks•YY1 interacts strongly with Trim28 in embryonic cells but less so in differentiated cells

SummaryEmbryonic cells transcriptionally repress the expression of endogenous and exogenous retroelements. Trim28, a key player in this silencing, is known to act in a large DNA-bound complex, but the other components of the complex are not fully characterized. Here, we show that the zinc finger protein Yin Yang 1 (YY1) is one such component. YY1 binds to the long terminal repeat (LTR) region of both exogenous and endogenous retroviruses (ERVs). Deletion of the YY1-binding site from the retroviral genome leads to a major loss of silencing in embryonic cells and a coordinated loss of repressive histone marks from the proviral chromatin. Depletion of YY1 protein results in marked upregulation of expression of exogenous viruses and of selected ERVs. Finally, we report an embryonic cell-specific interaction between YY1 and Trim28. Our results suggest a major role for YY1 in the silencing of both exogenous retroviruses and ERVs in embryonic cells.

Graphical AbstractFigure optionsDownload full-size imageDownload as PowerPoint slide