Odom:Research: Difference between revisions
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===Origin and impact of CTCF binding in mammals=== | ===Origin and impact of CTCF binding in mammals=== | ||
CCCTC-binding factor (CTCF) is a DNA-binding protein that can divide transcriptional and chromatin domains, help direct the location of cohesin, and orchestrate global enhancer-promoter looping. We are experimentally analyzing CTCF binding in tissues from many species of a cross section of mammalian orders to identify highly conserved and lineage-specific CTCF binding events. We, | CCCTC-binding factor (CTCF) is a DNA-binding protein that can divide transcriptional and chromatin domains, help direct the location of cohesin, and orchestrate global enhancer-promoter looping. We are experimentally analyzing CTCF binding in tissues from many species of a cross section of mammalian orders to identify highly conserved and lineage-specific CTCF binding events. We, and other labs, have identified that a major mechanism of CTCF binding evolution is carriage via SINE repeats. Newborn CTCF binding events often serve as both chromatin and gene expression barriers. Remarkably, fossilized repeat elements exist around over a hundred deeply shared CTCF binding events, indicating they originated from similar repeat driven expansions in a common mammalian ancestor hundreds of millions of years ago. Repeat-driven dispersal of CTCF binding is a fundamental, ancient, and still highly active mechanism of genome evolution in mammalian lineages. | ||
Revision as of 06:19, 17 September 2011
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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. We are particularly interested in understanding how a phenotype such as cell type transcription can be maintained in the face of genomic changes driven by evolution or cancer.
Ongoing Projects
Transcription and transcriptional regulatory evolution in mammals
Recent results suggests that few transcription factor-DNA interactions appear to be evolutionarily maintained in mammals, 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, continues to explore the regulatory mechanisms that can maintain specific transcriptional programs in spite of genetic evolutionary drift and subsequent divergence of transcription factor binding in vivo.
Determinants of tissue-specific transcriptional regulation
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.
Origin and impact of CTCF binding in mammals
CCCTC-binding factor (CTCF) is a DNA-binding protein that can divide transcriptional and chromatin domains, help direct the location of cohesin, and orchestrate global enhancer-promoter looping. We are experimentally analyzing CTCF binding in tissues from many species of a cross section of mammalian orders to identify highly conserved and lineage-specific CTCF binding events. We, and other labs, have identified that a major mechanism of CTCF binding evolution is carriage via SINE repeats. Newborn CTCF binding events often serve as both chromatin and gene expression barriers. Remarkably, fossilized repeat elements exist around over a hundred deeply shared CTCF binding events, indicating they originated from similar repeat driven expansions in a common mammalian ancestor hundreds of millions of years ago. Repeat-driven dispersal of CTCF binding is a fundamental, ancient, and still highly active mechanism of genome evolution in mammalian lineages.
