EVOGENETICSTFBINDING

Evolutionary genetics of transcription factor binding in closely related mammals

 Coordinatore THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE 

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 Nazionalità Coordinatore United Kingdom [UK]
 Totale costo 1˙910˙107 €
 EC contributo 1˙910˙107 €
 Programma FP7-IDEAS-ERC
Specific programme: "Ideas" implementing the Seventh Framework Programme of the European Community for research, technological development and demonstration activities (2007 to 2013)
 Code Call ERC-2013-CoG
 Funding Scheme ERC-CG
 Anno di inizio 2014
 Periodo (anno-mese-giorno) 2014-03-01   -   2019-02-28

 Partecipanti

# participant  country  role  EC contrib. [€] 
1    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

 Organization address address: The Old Schools, Trinity Lane
city: CAMBRIDGE
postcode: CB2 1TN

contact info
Titolo: Dr.
Nome: Duncan T
Cognome: Odom
Email: send email
Telefono: +44 1223769655
Fax: +44 1223769501

UK (CAMBRIDGE) hostInstitution 1˙910˙107.00
2    THE CHANCELLOR, MASTERS AND SCHOLARS OF THE UNIVERSITY OF CAMBRIDGE

 Organization address address: The Old Schools, Trinity Lane
city: CAMBRIDGE
postcode: CB2 1TN

contact info
Titolo: Ms.
Nome: Renata
Cognome: Schaeffer
Email: send email
Telefono: +44 1223 333543
Fax: +44 1223 332988

UK (CAMBRIDGE) hostInstitution 1˙910˙107.00

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mechanisms    tf    gene    micro    sites    genome    evolutionary    mouse    regulatory    conservation    differences    closely    mammals    genetic    binding    related    transcriptional    tissue    species    functional   

 Obiettivo del progetto (Objective)

'The genetic differences found in gene regulatory regions are the largest contributing factor to the diversity of phenotypes within and between mammalian species. However, the micro-evolutionary mechanisms active in closely-related species remain poorly explored, particularly in mammals. In Aim 1, we will exploit five recently sequenced mouse species to determine how often genetic sequence differences alter both the genome-wide binding and regulatory output of a core set of tissue-specific transcription factors (TFs) known to act combinatorially in liver. This project aim will establish the micro-evolutionary processes that drive interspecies changes in transcriptional regulation. In Aim 2, we will create first-generation intercrosses of a subset of these mouse species to dissect the cis and trans contributions to TF binding differences between species, and to explore the functional implications for nearby chromatin and gene expression. This aim will also establish whether any tissue-specific TF binding sites show parent-of-chromosomal origin effects. In Aim 3, we will use classically generated TF knockout mice to identify a set of functionally enriched TF binding sites, which will be further categorized by their conservation across the five mouse species. Then, using the revolutionary ability to rapidly and precisely delete individual binding sites (as well as combinations of binding sites) in the mouse genome by zinc finger nucleases, we will test whether conservation of these protein-DNA contacts can predict functional activity at target genes. This integrated approach combines the comparison of TF binding in closely-related mammals with powerful new experimental tools to afford a comprehensive understanding of the genetics and mechanisms underlying the micro-evolution of transcriptional regulatory networks.'

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