External Seminar Chromatin remodeling in development and disease Seminar details November 6, 2018, 12:00 pm @ Murray Seminar Room Dr. Peter Verrijzer, Erasmus University Medical Center, The Netherlands Host: Tom Owen-Hughes Abstract ATP-dependent chromatin remodeling complexes (remodelers) are abundant chromatin-associated molecular motors that mediate the assembly, sliding, restructuring, or ejection of nucleosomes. By modulating the presentation of target DNA elements, nucleosome dynamics provides a powerful and pervasive level of gene regulation. Rather than acting as general modulators of nucleosome dynamics, remodelers play surprisingly specific roles during development, and in human disease. However, the molecular basis of their specificity and the dynamics of chromatin remodeling remain poorly understood. We are interested in the role of remodelers in development and human cancer. Loss of the NURD subunit DOC1 is associated with human oral squamous cell carcinomas (OSCC). We found that DOC1 mediates the recruitment of NURD, affecting epigenetic reprogramming and transcription of selective genes. Our results revealed that NURD and SWI/SNF function antagonistically to control gene expression, through modulation of nucleosome remodeling and Polycomb recruitment. We propose that disturbance of this dynamic equilibrium may lead to defects in gene expression that promote oncogenesis. Using vital imaging, we have studied remodeler-chromatin interactions in the fruit fly. Our results suggest that the SWI/SNF remodeler uses a hit-and-run mechanism to continuously probe the genome. In particular, we have examined the role of ATP-hydrolysis in remodeler dynamics. We will discuss our latest findings concerning the mechanism of action of remodelers in development and in oncogenesis.
