Odom:Research

From OpenWetWare

(Difference between revisions)
Jump to: navigation, search
(Determinants of tissue-specific transcriptional regulation in a transplanted chromosome)
Line 1: Line 1:
{{Odom}}
{{Odom}}
-
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.
+
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==
==Ongoing Projects==
Line 6: Line 6:
===Transcription and transcriptional regulatory evolution in mammals===
===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.
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.
-
 
-
      '''Collaborators:''' Flicek/EBI, Blencowe/UToronto, Fraenkel/MIT, Gifford/MIT, Tavare/CRI
 
-
 
-
===noncoding RNA conservation and evolution===
 
-
We are also investigating the transcriptional regulation and evolution of numerous types of noncoding RNAs.  These riboregulators range from well-known classes such as microRNAs and transfer RNAs to more recently discovered species such as long intergenic noncoding RNAs.  We are applying approaches similar to those used in looking at transcrition factor binding evolution and transcriptional evolution of mRNAs to understanding how these additional layers of genomic regulation evolve.
 
-
      '''Collaborators:''' Brazma/EBI, Marioni/EBI, Ponting/Univ Oxford, Ule/LMB
 
===Determinants of tissue-specific transcriptional regulation===
===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.
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.
-
 
-
      '''Collaborators:''' Fisher/UCL, Tavare/CRI, Tybulewicz/NIMR
 

Revision as of 08:13, 17 September 2011

Odom laboratory

Home        Members        Research        Pubs        Protocols        Pix        Contact       


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.

Personal tools