Ronin Is Essential for Embryogenesis and the Pluripotency of Mouse ES Cells

Pluripotency is a unique biological state that allows cells to differentiate into any tissue in the body. Here we describe a novel candidate pluripotency factor, Ronin, that acts independently of canonical transcription factors and possesses a THAP domain, which is associated with sequence-specific DNA binding and epigenetic silencing of gene expression. Ronin is expressed primarily during the earliest stages of murine embryonic development, and its deficiency in mice produces periimplantational lethality and defects in the inner cell mass. Ronin ablation by a conditional knockout strategy prevents the growth of ES cells. Most critically, forced expression of Ronin allows ES cells to proliferate without differentiation under conditions that normally do not promote self-renewal, and it partly compensates for the effects of Oct4 knockdown. We demonstrate that Ronin binds directly to the HCF-1 protein, a key regulator of transcriptional control. Our findings identify Ronin as an essential factor underlying embryogenesis and ES cell pluripotency. Its direct binding to HCF-1 supports an epigenetic mechanism of gene repression in pluripotent cells.