The Death-Inducer Obliterator 1 (Dido1) Gene Regulates Embryonic Stem Cell Self-renewal [Gene Regulation]

December 17th, 2013 by Liu, Y., Kim, H., Liang, J., Lu, W., Ouyang, B., Liu, D., Songyang, Z.

The regulatory network of factors that center around master transcription factors such as Oct4, Nanog, and Sox2 help maintain embryonic stem (ES) cells and ensure their pluripotency. The target genes of these master transcription factors define the ES cell transcriptional landscape. In this study, we report our findings that Dido1, a target of canonical transcription factors such as Oct4, Sox2, and Nanog, plays an important role in regulating ES cell maintenance. We found that depletion of Dido1 in mouse ES cells led to differentiation, and ectopic expression of Dido1 inhibited differentiation induced by LIF withdrawal. We further demonstrated that while Nanog and Oct4 could occupy the Dido1 locus and promote its transcription, Dido1 could also target to the loci of pluripotency factors such as Nanog and Oct4 and positively regulate their expression. Through this feed-back and feed-forward loop, Dido1 is able to regulate self-renewal of mouse ES cells.___________