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Conservation and Divergence of Tissue-Specific Transcriptional Regulation

Objective

Vertebrates contain hundreds of different cell types which maintain phenotypic identity by a combination of epigenetic programming and genomic regulation. Systems biology approaches are now used in a number of laboratories to determine how transcription factors and chromatin marks pattern the human genome. Despite high conservation of the cellular and molecular function of many mammalian transcription factors, our recent experiments in matched mouse and human tissues indicates that most transcription factor binding events to DNA are very poorly conserved. A hypothesis that could account for this apparent divergence is that the larger regional pattern of transcription factor binding may be conserved. To test this, (1) we are characterizing the global transcriptional profile, chromatin state, and complete genomic occupancy of a set of tissue-specific transcription factors in hepatocytes of strategically chosen mammals; (2) to further identify the precise mechanistic contribution of cis and trans effects, we are comparing transcription factor binding at homologous regions of human and mouse DNA in a mouse line that carries human chromosome 21. Together, these projects will provide insight into the general principles of how transcriptional networks are evolutionarily conserved to regulate cell fate specification and function using a clinically important cell type as a model.

Field of science

  • /natural sciences/biological sciences/genetics and heredity/chromosome
  • /natural sciences/biological sciences/zoology/mammalogy
  • /natural sciences/biological sciences/genetics and heredity/genome

Call for proposal

ERC-2007-StG
See other projects for this call

Funding Scheme

ERC-SG - ERC Starting Grant

Host institution

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 99 670,82
Principal investigator
Duncan Odom (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)

Beneficiaries (2)

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
United Kingdom
EU contribution
€ 99 670,82
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
Activity type
Higher or Secondary Education Establishments
Principal investigator
Duncan Odom (Dr.)
Administrative Contact
Renata Schaeffer (Ms.)
CANCER RESEARCH UK LBG
United Kingdom
EU contribution
€ 860 329,18
Address
St John Street 407 Angel Building
EC1V 4AD London
Activity type
Research Organisations
Administrative Contact
Emma Ryley (Dr.)