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Nat Genet. 2017 Jun;49(6):925-934. doi: 10.1038/ng.3844. Epub 2017 May 1.

Conserved roles of mouse DUX and human DUX4 in activating cleavage-stage genes and MERVL/HERVL retrotransposons.

Author information

1
Department of Oncological Sciences, Huntsman Cancer Institute and Howard Hughes Medical Institute, Salt Lake City, Utah, USA.
2
Departments of Obstetrics and Gynecology, and Surgery, University of Utah School of Medicine, Salt Lake City, Utah, USA.
3
Division of Human Biology, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

Abstract

To better understand transcriptional regulation during human oogenesis and preimplantation development, we defined stage-specific transcription, which highlighted the cleavage stage as being highly distinctive. Here, we present multiple lines of evidence that a eutherian-specific multicopy retrogene, DUX4, encodes a transcription factor that activates hundreds of endogenous genes (for example, ZSCAN4, KDM4E and PRAMEF-family genes) and retroviral elements (MERVL/HERVL family) that define the cleavage-specific transcriptional programs in humans and mice. Remarkably, mouse Dux expression is both necessary and sufficient to convert mouse embryonic stem cells (mESCs) into 2-cell-embryo-like ('2C-like') cells, measured here by the reactivation of '2C' genes and repeat elements, the loss of POU5F1 (also known as OCT4) protein and chromocenters, and the conversion of the chromatin landscape (as assessed by transposase-accessible chromatin using sequencing (ATAC-seq)) to a state strongly resembling that of mouse 2C embryos. Thus, we propose mouse DUX and human DUX4 as major drivers of the cleavage or 2C state.

PMID:
28459457
PMCID:
PMC5703070
DOI:
10.1038/ng.3844
[Indexed for MEDLINE]
Free PMC Article

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