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MD Anderson Events

John H. Blaffer Lecture Series

John H. Blaffer Lecture Series

   Scott W. Hiebert, Ph.D.

Professor
Vanderbilt University School of Medicine
Nashville, TN
 
 
“Histone deacetylase 3 regulates chromatin structure, gene expression and DNA replication, but is it a good therapeutic target?”
 
 
Host: Michelle Barton
Biochemistry & Molecular Biology

Date: 11/13/12, 4pm to 5pm
Time: 11/13/12, 4pm to 5pm
Location: Onstead Auditorium, Basic Science Research Building, Floor 3, near Elevator J, (S3.8012)
Format: Lecture
CME: 0
Facilitator: Les Krushel
Speaker: Scott W. Hiebert
Speaker Bio: The work in my laboratory focuses on determining the normal function of the AML1/RUNX1 transcription factor in the regulation of hematopoietic gene expression and the mechanism by which the t(8;21), inv(16), and the t(12;21) chromosomal translocations disrupt normal AML-1 function to promote acute leukemia. We have defined AML-1 as a transcription factor that binds the "enhancer core" motif, which regulates the expression of a large number of tissue specific genes. Transcriptional studies demonstrated that AML1 both activates and represses transcription, and that the translocation fusion proteins inhibit expression of AML1-dependent target genes. We have determined that the t(8;21) fusion protein, AML1/ETO, interacts with the mSin3 and nuclear hormone co-repressors that recruit histone deacetylases to repress transcription. This initial observation led us to demonstrate that the t(12;21) and inv(16) proteins also associate with co-repressors and histone deacetylases. Thus, we have identified a common mechanism for transcriptional repression for these three translocations. Given that these fusion proteins repress transcription and cause cancer, we asked whether they inhibit the expression of known tumor suppressor genes. We have identified 2 tumor suppressors that are regulated by these translocation fusion proteins (p19ARF and Neurofibromatosis-1), which regulate the p53 tumor suppressor and the Ras oncogene, respectively. We continue to use mouse models to dissect the molecular mechanisms by which these chromosomal translocation fusion proteins trigger acute leukemia
Contact: Doris Green - 46267 - dlgreen1@mdanderson.org