The Department of Biological Sciences Seminar Series is pleased to welcome Dr. Lizhao Yu, an Assistant Professor in the Department of Microbiology and Molecular Genetics at Rutgers, New Jersey Medical School- Cancer Center.
Retinoblastoma Tumor Suppressor Plays an Unorthodox Role to Promote DNA Replication in Terminally Differentiating Cells
"Rb plays a critical role in ensuring permanent cell cycle exit in cells undergoing terminal differentiation. A hallmark phenotype of Rb-deficiency in terminally differentiating cells is increased fraction of S-phase cells, which is believed to be resulted from unscheduled DNA replication and untimely cell cycle entry. Here we show that during erythroid terminal differentiation, Rb plays a previously unappreciated and unorthodox role in promoting DNA replication. Specifically, inactivation of Rb in erythroid cells led to inefficient DNA replication, increased DNA damage, and prolonged cell cycle progression, culminating in defective terminal differentiation. Importantly, all of these defects associated with Rb loss were exacerbated by concomitant inactivation of E2f8, leading to severe anemia. Gene expression profiling and chromatin immunoprecipitation (ChIP) revealed that Rb and E2f8 co-suppressed E2f-target genes that are critical for DNA replication, DNA damage response, DNA repair, and cell cycle progression. Remarkably, inactivation of E2f2 substantially ameliorated the erythropoietic defects and reversed aberrant gene expression observed in the Rb;E2f8 double knockout mice. Importantly, despite a lack of transcriptional regulation of E2f2 by Rb or E2f8, inactivation of Rb and E2f8 synergizes to increase E2f2 binding to its target gene promoters, leading to the untimely activation of E2f targets. We propose that Rb and E2F8 synergize to promote efficient DNA replication and erythroid terminal differentiation by preventing E2f2-mediated transcriptional activation through the ability of Rb to sequester E2f2, and the ability of E2f8 to compete with E2f2 for E2f binding sites on the promoters of E2f-target genes.Climate change is causing environmental temperatures to rise across the globe. But despite the global scale of this phenomenon, organisms experience climate change at the local level. Using tropical Anolis lizards as a model system, I will outline my research on the susceptibility of ectotherms to warming based on fine-scale measurements of changes in habitat conditions and detailed descriptions of how the animals respond. I focus on the physiological, behavioral, and evolutionary mechanisms that may allow populations to persist in the face of global change."
This seminar is hosted by Dr. Charlie Wei (email@example.com.)
As usual, all seminars in our series are free and open to any interested public. Please visit our seminar calendar for more information and other events. http://www.clemson.edu/cafls/departments/biosci/research/seminars.html
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