Odom:Research: Difference between revisions
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===Conservation of master regulator targeting through evolution=== | ===Conservation of master regulator targeting through evolution=== | ||
Recent results suggests that few transcription factor-DNA interactions appear to be evolutionarily maintained, yet most evidence suggests that the gene expression programs of particular tissues are highly conserved. My laboratory, in collaboration with | Recent results suggests that few transcription factor-DNA interactions appear to be evolutionarily maintained, yet most evidence suggests that the gene expression programs of particular tissues are highly conserved. My laboratory, in collaboration with a number of other laboratories (Fraenkel/MIT, Gifford/MIT, Flicek/EBI, Tavare/CRI) is continuing to explore the regulatory mechanisms that afford specific transcriptional programs resistance to evolutionary drift, despite surprisingly large changes in the binding of regulators. | ||
===miRNA functional genomics=== | ===miRNA functional genomics=== | ||
Revision as of 10:21, 5 May 2008
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Odom laboratory
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In general, we take an integrative approach, combining genome-wide transcription factor binding, gene expression perturbation using genetic manipulations, comparative genomics, and physiological approaches to understand on a systems-wide basis how a tissue is defined. To date, our work has revealed the core circuitry of human hepatocytes and pancreatic islets, begun assessing how small collections of transcriptional regulators can dictate cellular biology, and preliminarily revealed the connections that exist between miRNA programs and transcription factor binding events.
Ongoing Projects
Conservation of master regulator targeting through evolution
Recent results suggests that few transcription factor-DNA interactions appear to be evolutionarily maintained, yet most evidence suggests that the gene expression programs of particular tissues are highly conserved. My laboratory, in collaboration with a number of other laboratories (Fraenkel/MIT, Gifford/MIT, Flicek/EBI, Tavare/CRI) is continuing to explore the regulatory mechanisms that afford specific transcriptional programs resistance to evolutionary drift, despite surprisingly large changes in the binding of regulators.
miRNA functional genomics
One practical output of these studies is the identification of candidate miRNAs which may be involved in tissue-specific transcriptional regulation downstream of known tissue-specific transcription factors. Because of their recent discovery, little is known about the regulation of, function of, and downstream programs controlled by miRNAs. We are applying similar approaches to understanding these additional layers of regulation.
Determinants of tissue-specific transcriptional regulation in a transplanted chromosome
Sets of conserved transcription factors are responsible for conserved tissue-specific transcription, yet transcription factor binding events diverge rapidly between closely related species. To decouple the distinct molecular mechanisms that direct transcription factor binding and gene expression we investigated tissue-specific transcriptional regulation in a mouse containing human chromosome 21 (the Tc1 mouse). Gene expression and transcription intiation occurs at similar syntenic genes in hepatocytes from humans, wild-type mice, and Tc1 mice; however, the transcription initiation occurring in other genomic regions is specified by species-specific genetic sequences. Characterization of transcription factor binding in the Tc1 mice reveals that tissue-specific transcriptional regulation is directed almost exclusively by species-specific genetic sequences. Divergent patterns of transcriptional regulation coded in genetic sequence can thus be transplanted between species to recapitulate conserved transcription in homologous tissues.
