The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation.

Development (Cambridge, England) 2016 Oct 01

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Leucine twenty homeobox (LEUTX) is a paired (PRD)-like homeobox gene that is expressed almost exclusively in human embryos during preimplantation development. We previously identified a novel transcription start site for the predicted human LEUTX gene based on the transcriptional analysis of human preimplantation embryos. The novel variant encodes a protein with a complete homeodomain. Here, we provide a detailed description of the molecular cloning of the complete homeodomain-containing LEUTX Using a human embryonic stem cell overexpression model we show that the complete homeodomain isoform is functional and sufficient to activate the transcription of a large proportion of the genes that are upregulated in human embryo genome activation (EGA), whereas the previously predicted partial homeodomain isoform is largely inactive. Another PRD-like transcription factor, DPRX, is then upregulated as a powerful repressor of transcription. We propose a two-stage model of human EGA in which LEUTX acts as a transcriptional activator at the 4-cell stage, and DPRX as a balancing repressor at the 8-cell stage. We conclude that LEUTX is a candidate regulator of human EGA. © 2016. Published by The Company of Biologists Ltd.

Citation

Eeva-Mari Jouhilahti, Elo Madissoon, Liselotte Vesterlund, Virpi Töhönen, Kaarel Krjutškov, Alvaro Plaza Reyes, Sophie Petropoulos, Robert Månsson, Sten Linnarsson, Thomas Bürglin, Fredrik Lanner, Outi Hovatta, Shintaro Katayama, Juha Kere. The human PRD-like homeobox gene LEUTX has a central role in embryo genome activation. Development (Cambridge, England). 2016 Oct 01;143(19):3459-3469