Pou5f1 Transcription Factor Controls Zygotic Gene Activation In Vertebrates

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Science  30 Aug 2013:
Vol. 341, Issue 6149, pp. 1005-1009
DOI: 10.1126/science.1242527

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Pluripotency Control

The transcription factors Pou5f1/Oct4, Sox2, and Nanog play central roles in pluripotency control in mammalian embryonic stem (ES) cells. The evolution of the pluripotency regulatory network and its roles during early development of nonmammalian vertebrates is unknown. Leichsenring et al. (p. 1005, published online 15 August) show that in zebrafish embryos, Pou5f1 controls priming and transcriptional activation of the first zygotically expressed genes. This mechanism for transition from the transcriptionally silent cleavage stage to the transcriptionally active blastula stage may have evolved to control the prolonged cell pluripotency state in mammalian early development and ES cells, establishing a link between zygotic gene activation and pluripotency control.


The development of multicellular animals is initially controlled by maternal gene products deposited in the oocyte. During the maternal-to-zygotic transition, transcription of zygotic genes commences, and developmental control starts to be regulated by zygotic gene products. In Drosophila, the transcription factor Zelda specifically binds to promoters of the earliest zygotic genes and primes them for activation. It is unknown whether a similar regulation exists in other animals. We found that zebrafish Pou5f1, a homolog of the mammalian pluripotency transcription factor Oct4, occupies SOX-POU binding sites before the onset of zygotic transcription and activates the earliest zygotic genes. Our data position Pou5f1 and SOX-POU sites at the center of the zygotic gene activation network of vertebrates and provide a link between zygotic gene activation and pluripotency control.

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