Event Scheduled for Feb 19, 2013
Event: CSE Colloquium Series - Logan Everett "Integrative genomic analysis of CREB defines a critical role for transcription factor cooperation in mediating the fed/fasted switch in liver"
Location: ITE 336
Time: 01:15 pm
Details of Event:
Metabolic homeostasis in mammals critically depends on the regulation of fasting-induced genes by the transcription factor CREB in the liver. Previous genome-wide analysis has shown that only a small percentage of CREB target genes are induced in response to fasting-associated signaling pathways. The precise molecular mechanisms by which CREB specifically targets these genes in response to alternating hormonal cues remain to be elucidated. Using data from chromatin immunoprecipitation coupled to high-throughput sequencing (ChIP-seq), I quantitatively compared the extent of CREB-DNA interactions in livers from both fasted and fed mice. This analysis demonstrated that CREB remains constitutively bound to its target genes in the liver regardless of the metabolic state, revealing a role for additional factors in specifying fasting-induced CREB target genes. Additionally, I developed a novel, robust framework for filtering ChIP-seq peaks, termed the ‘single sample independence’ (SSI) test that greatly reduced the number of false positive peaks, while still identifying thousands of novel CREB target genes. Integration of the CREB ChIP-seq data with expression microarray data and additional ChIP-seq data sets revealed that fasting-induced genes are specifically associated with complex regulatory elements bound by both CREB and additional transcription factors. Our results support a model in which CREB is constitutively bound to thousands of potential target genes and combinatorial interactions between DNA-binding factors are necessary to achieve the specific transcriptional response of the liver to fasting. The methods applied in this work can be used more broadly to explore the role of transcription factor cooperation in shaping the overall transcriptional regulatory network of the cell.
Target Audience: Open to All
Sponsored By: Computer Science and Engineering
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