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Learn MoreUTX/KDM6A is known to promote open chromatin structure to facilitate gene activation. Although UTX is important for normal and cancer development, its molecular activities in developmental gene regulation remain unclear. Using genetic knockout of UTX in human embryonic stem cells, we show that UTX promotes human pluripotency and suppresses neural differentiation. In human neural stem cells (hNSCs), UTX modulates self-renewal, is required for neuronal differentiation, and suppresses glial/astrocytic differentiation by positively and negatively regulating its target genes. 70% of UTX-occupied regions are associated with epigenetic modifications known to be influenced by UTX, and UTX knockout leads to significant changes in expression of more than 50% of its target genes but epigenetic changes in less than 6% of its target genes. UTX likely affects gene expression via alternative molecular activities in hNSCs. Our findings reveal new functions of UTX in gene regulation and cell fate decisions in human stem cells. SOURCE: Beisi Xu (beisi.xu@stjude.org) - St Jude Children's Research Hosipital
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