Identification of target genes of the transcription factor Zfx in embryonic stem cells

Self-renewal is the defining property of all stem cells, allowing these cells to proliferate without loosing differentiation potential. Because embryonic and adult stem cells exhibit strikingly different anatomical and molecular features, it was though that independent genetic pathways controlled their self-renewal. Recent work from our laboratory showed that the transcription factor Zfx is necessary for the self-renewal of embryonic and hematopoietic stem cells (ESC and HSC, respectively), suggesting a common genetic pathway in embryonic and adult stem cell self-renewal. To dissect the molecular basis of Zfx in stem cell self-renewal, we used global expression analysis and genome-wide chromatin immunoprecipitation to identify transcriptional targets of Zfx. Zfx activated the expression of a common set of target genes in ESC and HSC, demonstrating the common regulation of stem cell self-renewal. Zfx regulates the expression of two regulators of ESC self-renewal, Tbx3 and Tcl1, showing that it simultaneously controls pathways required for ESC self-renewal. Our analyses identified several novel target genes of Zfx in stem cells and differentiated tissues, increasing our understanding of the molecular mechanism of Zfx. Finally, Smoothened, the hedgehog (Hh) signaling transducer, is a direct target of Zfx, suggesting a role for Zfx in Hh signaling.