THE BLYTHE LAB
Laboratory of Embryonic Development and the Regulation of Gene Expression in the Department of Molecular Biosciences, Northwestern University
and the NSF/Simons National Institute for Theory and Mathematics in Biology
In the Blythe Lab, we study how the embryonic genome 'wakes up' for first time and begins directing the process of cell fate specification. This unique moment in development gives us the opportunity to study how the fundamental features of chromatin structure are built from the ground up.
Current Areas of Interest
ZYGOTIC GENOME ACTIVATION
Every embryo activates its genome at a precise time following fertilization. This depends on biological timing mechanisms that count the amount of DNA relative to the overall cytoplasmic volume. We are interested in understanding the molecular clocks that govern this critical developmental milestone.
This movie shows Drosophila chromatin in red and the formation of the nucleolus after the 13th mitotic division, labeled with RNA Polymerase I, in green. This is one of the many events that occur, like clockwork, during Zygotic Genome Activation.
Read about formation of the nucleolus here.
SHAPING AND RE-SHAPING THE EPIGENETIC LANDSCAPE
To activate, the zygotic genome must first build the initial, 'ground state' of chromatin structure to support the first gene expression events. To the best of our understanding, this is driven by a collection of specialized proteins termed "pioneer factors". Once the genome awakens, biological systems operate on the ground state to create cell-type specific chromatin states. We are interested in knowing how pioneers shape and re-shape chromatin states from the very beginning of development.
The movie above is an animation based on the data in this paper. It shows the degree of chromatin accessibility as measured by ATAC-seq at the hunchback locus over the last three cell divisions prior to ZGA. Explore the complete dataset here.
GENE REGULATORY NETWORK FUNCTION
Gene regulatory networks allow biological systems to accomplish complex tasks, like specifying developmental lineages. While these are driven by transcription factors and DNA regulatory elements, it is unclear how transcription factors contend with chromatin states to carry out network function. We are interested in understanding the interface between chromatin state and network function.
The movie above shows the expression of the pair-rule gene even-skipped using a recently developed approach. We have demonstrated how another pair-rule gene, odd-paired, functions as a pioneer in the pair-rule network. Read about it here.
2200 Campus Drive
Evanston, IL 60208
Department of Molecular Biosciences
2205 Tech Dr., Hogan
Evanston, IL 60208
shelby.blythe [at] northwestern.edu
+1-847-491-4062 (office), +1-847-467-3454 (lab)