| Description | Molecular Engineering and Sciences Seminar Series
Controlling, measuring, and modelling epigenetic regulation dynamics
Abstract: Chromatin-mediated regulation changes dynamically over time and often shows cell-to-cell heterogeneity. To get at the basic principles of chromatin regulation dynamics at the single-cell level and test different epigenetic editing tools that could correct faulty chromatin states, we target genes using fusions between DNA binding domains and chromatin regulator domains, and measure expression of the target genes over time using time-lapse microscopy and flow cytometry. Using these methods, we discovered that silencing initiated by recruiting a KRAB domain at an upstream gene spreads to the downstream gene across different insulator elements and across 5000bp of spacer DNA. Surprisingly, we observe spreading of silencing not only with domains classically associated with classical heterochromatin such as KRAB, but also with domains that remove histone acetylation, such as HDAC4. Epigenetic memory and reactivation of the two nearby genes is also highly coupled at the single-cell level, suggesting that active gene expression states can also spread. Dissecting the factors that influence the speed of spreading associated with different chromatin pathways can help us understand chromatin regulation and epigenetic memory quantitatively, and develop more predictive tools to fix it when it is miss-regulated in disease.
This weekly seminar brings together students, faculty and invited guests from various disciplines across campus to explore current trends in molecular engineering and nanotechnology. It is a forum for active interdisciplinary discussions. These talks are open to the public and attract a diverse audience of students and faculty. |
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