Abstract
Undifferentiated embryonic cell transcription factor 1 (Utf1) is expressed in pluripotent embryonic stem cells (ESCs) and primordial germ cells (PGCs). Utf1 expression is directly controlled by pluripotency factors Oct4 and Sox2, which form a ternary complex with the Utf1 enhancer. The Utf1 protein plays a role in chromatin organization and epigenetic control of bivalent gene expression in ESCs in vitro, where it promotes effective cell differentiation during exit from pluripotency. The function of Utf1 in PGCs in vivo, however, is not known. Here, we report that proper development of Utf1 null embryos almost entirely depends on the presence of functional Utf1 alleles in the parental germline. This indicates that Utf1’s proposed epigenetic role in ESC pluripotency in vitro may be linked to intergenerational epigenetic inheritance in vivo. One component - or at least facilitator - of the relevant epigenetic mark appears to be Utf1 itself, since Utf1-driven tomato reporter and Utf1 are detected in mature germ cells. We also provide initial evidence for a reduced adult testis size in Utf1 null mice. Our findings thus point at unexpected functional links between the core ESC pluripotency factor network and epigenetic inheritance of pluripotency.
Highlights
Undifferentiated embryonic cell transcription factor 1 (Utf1) is expressed in pluripotent embryonic stem cells (ESCs) and primordial germ cells (PGCs)
General interest in Utf[1] resulted from the demonstration that Utf[1] expression in mouse and human cells is directly regulated by core pluripotency factors Oct[4], Sox[2], and most likely Nanog, which form a ternary complex with the Utf[1] enhancer[4,5,6]
We expect that the embryonic development phenotype should become detectable in F1 homozygous wild-type Utf1(+/+) embryos generated by Utf1(−/+)-tomato mice[29]
Summary
Undifferentiated embryonic cell transcription factor 1 (Utf1) is expressed in pluripotent embryonic stem cells (ESCs) and primordial germ cells (PGCs). A number of molecular functions have been assigned to Utf[1] in ESCs, such as transcription factor[1], chromatin organizer[12], and epigenetic factor controlling H3K27me[3] deposition at bivalent genes via binding to thousands of loci around transcriptional start sites[13] The latter is interesting because it connects the pluripotency core to the polycomb-repressive complex 2 (PRC2) network, and the deposition of epigenetic chromatin marks in ESCs. The latter is interesting because it connects the pluripotency core to the polycomb-repressive complex 2 (PRC2) network, and the deposition of epigenetic chromatin marks in ESCs These data, in conjunction with Utf[1] knock-down (kd) and knock-out (ko) mouse ESCs studies, pointed at an important regulatory role for Utf[1] during exit from ESC pluripotency en route to effective cell differentiation[12,13]. We made an interesting initial finding that hinted at a negative correlation between adult testis vascularization and size with the Utf1(−/−)
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