View Program - 63rd Annual Drosophila Research Conference

Precise and coordinated regulation of gene expression during growth and development is essential for the viability of all organisms and to prevent diverse diseases ranging from cancer to neurodegeneration. Chromatin domains coordinate gene expression by concentrating key factors at specific genomic locations in a context-specific way to concordantly activate or repress groups of genes. Before zygotic genome activation (ZGA), chromatin domains have not yet formed and only a few key transcription factors (TFs) are bound which are called pioneer TFs. Pioneer TFs have the ability to bind to closed chromatin, recruit chromatin remodelers to open chromatin, and target additional transcription complexes. Furthermore, pioneer TFs are critical for cellular reprogramming and are often reactivated in cancer. Pioneer TFs can regulate the formation of active and repressive chromatin domains which form after ZGA. However, the fundamental mechanisms by which chromatin domains are formed at the correct genomic locations across time and space remain unknown. One example of a conserved active chromatin domain is the hyperactivated single male X-chromosome in Drosophila, which coordinately upregulates thousands of genes two-fold to equalize transcript levels with the two autosomes. My preliminary data suggest that the interaction between an essential pioneer TF and large transcription complex is important to target this active chromatin domain specifically to the X-chromosome. Therefore, I will use genomic, optogenetic, and machine learning approaches to define new mechanisms by which a pioneer TF nucleates the formation of an active chromatin domain that upregulates the male X-chromosome over time and space.

X marks the spot: Specifically targeting active chromatin to the X chromosome