Abstract

In this seminar, I will discuss my lab’s work on how chromatin structure constrains the gene regulatory networks that pattern the embryo, and how changes to chromatin structure are encoded within these developmental repertoires. By measuring changes to chromatin accessibility patterns in early Drosophila embryos, we find that accessibility states change on a timescale of minutes, and are influenced not only by cell cycle progression but also signaling inputs for cell fate specification. What this means is that the complete cis-regulatory landscape for certain developmental routines such as embryonic segmentation are established gradually, in a step-wise manner dependent on passage through prior regulatory states. Encoded within these regulatory networks are specialized transcription factors known as Pioneers that, once activated, modulate accessibility patterns to accommodate later steps in the process. Importantly, altering the temporal order of these changes disrupts the fidelity of segmentation, supporting the idea that the temporal sequence of chromatin accessibility states plays a deterministic role in the developmental program.

This work has led us to investigate how transcription factors contend with binding DNA in the chromatin context. I will also present unpublished empirical and modeling work to address how competition with nucleosomal substrates likely sets concentration thresholds critical for the function of the Bicoid morphogen gradient.