Chromosomes in 3D
The developmentally dynamic nucleus
How are chromosomes organized within nuclei? And how does organization impact developmental events? The nucleus is very dynamic during embryogenesis, in part because heterochromatin is made de novo, as shown below for young, pre-gastrula embryos. One goal is to understand how the nucleus changes, what factors regulate the process and why it matters to animals. Recently we discovered a complex that times the onset of heterochromatin, which you can read about here *
In addition, we are addressing these questions by tracing chromosomes with multiplex FISH (fluorescence in situ hybridization) in intact C. elegans.
FISH probes are designed against a region of interest, and rounds of FISH imaging allow us to track the conformation of chromosomes in intact animals. We can calculate the folding properties and also examine mutants to see how they impact normal folding. From these sorts of analyses we’ve learned that worm chromosomes look like a barbell, with a lot of folding in the ‘arm’ regions and less in the center. Below is an example of what a wild-type chromosome looks like. We now will apply this method to a range of biological questions such as how do these structures change during development.
* Mutlu et al., Regulated nuclear accumulation of a histone methyltransferase times the onset of heterochromatin formation in C. elegans embryos. Science Advances, 2018 here.
Mutlu et al. MET-2, a SETDB1 family methyltransferase, coordinates embryo events through distinct histone H3 methylation states. BioRxiv here
What got us started:
Yuzyuk et al. The Polycomb Complex Protein mes-2/E(z)Promotes the Transition from Developmental Plasticity to Differentiation in C. elegans Embryos. Dev Cell, 2009 here
Photo: Frederick Blichert dgit.com, David Hall, Ahilya Sawh