Maintenance of stem cell self-renewal by sex chromosomal zinc-finger transcription factors.

In this Editorial review, we would like to focus on a very recent discovery showing the global autosomal gene regulation by Y- and inactivated X-chromosomal transcription factors, zinc finger gene on the Y chromosome (ZFY) and zinc finger protein X-linked (ZFX). ZFX and ZFY are both zinc-finger proteins that encode general transcription factors abundant in hematopoietic and embryonic stem cells. Although both proteins are homologs, interestingly, the regulation of self-renewal by these transcriptional factors is almost exclusive to ZFX. This fact implies that there are some differential roles between ZFX and ZFY in regulating the maintenance of self-renewal activity in stem cells. Besides the maintenance of stemness, ZFX overexpression or mutations may be linked to certain cancers. Although cancers and stem cells are double-edged swords, there is no study showing the link between ZFX activity and the telomere. Thus, stemness or cancers with ZFX may be linked to other molecules, such as Oct4, Sox2, Klf4, and others. Based on very recent studies and a few lines of evidence in the past decade, it appears that the ZFX is linked to the canonical Wnt signaling, which is one possible mechanism to explain the role of ZFX in the self-renewal of stem cells.