Embryonic genome activation (EGA) is a key event in the development of all organisms – when zygotic transcription takes over from maternally provided mRNAs. Relatively little is known about the control of EGA in human embryos, which occurs at the 4- to 8-cell stage. Juha Kere and colleagues have previously found that many paired-like homeobox transcription factors are expressed in the early human embryo, and identified a 36 bp motif associated with genes upregulated at the EGA. In a follow-up study (p. 3459), the authors now characterise one of these factors, LEUTX, in more detail. LEUTX is specifically expressed in early human embryos and cell lines derived from early blastomeres, with barely detectable or absent expression in later embryos, other tissues or cell lines. The authors then use expression profiling to analyse the consequences of overexpressing LEUTX in human embryonic stem cells. LEUTX induces expression of a large number of targets, including several pluripotency-associated genes. Intriguingly, the previously identified EGA-associated 36 bp motif is significantly enriched in the LEUTX-regulated gene set; in reporter assays, LEUTX can bind this motif and promote expression. A second paired-like homeobox factor, DPRX, is a putative target of LEUTX, and in turn, appears to bind the same motif and repress transcription. The authors therefore propose a two-stage model for EGA – whereby LEUTX-mediated induction followed by DPRX-mediated repression leads to transient expression of key EGA genes.
- © 2016. Published by The Company of Biologists Ltd