Melanie D. White, Juan F. Angiolini,
Yanina D. Alvarez, Ziqing Zhao, Stephanie Bissiere,
Valeria Levi, Nicolas Plachta
Published in Cell on 24 March 2016.
The group led by Nicolas Plachta (IMCB, A*STAR) developed imaging technologies to study
how transcription factors (the proteins that control gene expression) bind to DNA in live
mouse embryos. They used mouse embryos as these resemble almost perfectly the human
embryo, and imaged them without perturbing their development.
Immediately after fertilization, the newly created 'single-cell' embryo starts to divide to
create a multicellular organism. But exactly when and how its cells adopt their first
differentiated fate has long been a mystery. The team discovered differences in the way some
transcription factors bind to their DNA target genes between the cells of the early embryo.
They showed that more stable interactions between some transcription factors and their
targets actually predict the fate of the cells later on.
The findings promote a revision of classic models of embryo development. They may also
help design more efficient strategies for screening human embryos for assisted reproduction
and genetic diagnoses. Clinicians routinely remove cells from human embryos and analyze
them for genetic defects, but it remains problematic to decide which of these embryos may
be more successful when transplanted back in to the uterus. An important future goal is to
detect abnormalities in single cells without physical manipulation. The development of this
type of technologies to image single cells in intact embryos is a step forward in this direction.
Figure legend: Quantification of the dynamics of Sox2-
DNA binding in single cells of live mouse
embryos shows that its heterogeneities in
four-cell blastomeres are regulated by
histone methylation and predict a bias in
the contribution of cells to the inner mass.
- Transcription factors display temporally distinct DNA
binding in live mouse embryos
- Sox2-DNA binding is heterogeneous between four-cell
blastomeres within the embryo
- Histone 3 arginine 26 methylation regulates Sox2-DNA
- More Sox2 engaged in long-lived DNA binding predicts inner
For more information on Nicolas PLACHTA 's lab, please click here.