Journal
DEVELOPMENT
Volume 143, Issue 19, Pages 3459-3469Publisher
COMPANY BIOLOGISTS LTD
DOI: 10.1242/dev.134510
Keywords
Embryo genome activation; Homeobox gene; Preimplantation development; Embryonic stem cells
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Funding
- Karolinska Institutet's Distinguished Professor Award
- Karolinska Institutet's Research Foundation
- Swedish Research Council (Vetenskapsradet)
- Strategic Research Program for Diabetes at Karolinska Institutet
- EU [324509]
- ALF (Stockholm County and Karolinska Institutet)
- Ragnar Soderberg Foundation (Ragnar Soderbergs Stiftelse)
- Swedish Foundation for Strategic Research (Stiftelsen for Strategisk Forskning)
- Ake Wiberg Foundation (Ake Wiberg Stiftelse)
- Jane & Aatos Erkko Foundation (Jane ja Aatos Erkon Saatio)
- Orion Research Foundation (Orionin Tutkimussaatio)
- Mats Sundin Fellowship in Development and Health
- Ake Wiberg and Magnus Bergvall Foundation (Magnus Bergvalls Stiftelse)
- Knut and AliceWallenberg Foundation (Knut och Alice Wallenbergs Stiftelse) [KAW 20015.0096]
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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.
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