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Cancer Research UK Cambridge Institute

Group Leader

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The work we and our collaborators have performed has challenged and refined current understanding of mammalian genome evolution, and what functional implications this rapid evolution has for human health and disease.

Research in the Odom laboratory has revealed that most transcription factor binding diverges rapidly between closely related species, and that relationships between TF functionality and conservation of binding among five diverse vertebrates are complex and unpredictable. We have explored how repetitive element expansions have been actively remodeling the genomes of most mammalian lineages for hundreds of millions of years by carrying CTCF binding into tens of thousands of new locations. By investigating how RNA polymerase III regulates tRNAs in multiple mammals, we have discovered that the polymerases responsible for gene expression appear to be under constraint at the level of their transcripts, the mechanism for which we are actively investigating. More recently, we have profiled how enhancers and promoters change in twenty species from across the mammalian clade.

Perhaps most profoundly, we showed that DNA sequence variation is the ultimate driver of this evolution, using a previously existing mouse model of Down syndrome which carries human chromosome 21, to place human genetic sequence into mouse diet, lifestyle, epigenetic machineries, developmental processes, and nuclear concentration of transcription factors. We found that all levels of transcriptional control (including transcription factor binding, histone marks, and gene expression) are primarily controlled by the underlying genetic sequence in homologous tissues, because the mouse nucleus perfectly recreates human transcription and transcriptional regulation on nonrepeat sequences of HsChr21.

 

FIVE SELECTED PUBLICATIONS

D. Villar, C. Berthelot, S. Aldridge, T. Rayner, M. Lukk, M. Pignatelli, T. Park, R. Deaville, J. Erichsen, A. Jasinska, J. Turner, M. Bertelsen, E. Murchison, P. Flicek, D. T. Odom.
“Enhancer evolution across twenty mammalian species,” Cell 160 (2015) 554-563.

K. Stefflova, D. Thybert, M. Wilson, I. Streeter, J. Aleksic, P. Karagianni, A. Brazma, D. Adams, J. Marioni, P. Flicek, D. T. Odom.
“Cooperativity and rapid evolution of co-bound transcription factors in closely related mammals,” Cell 154 (2013) 530-540.

D. Schmidt, P. Schwalie, M. D. Wilson, B. Ballester, A. Goncalves, C. Kutter, G. Brown, A. Marshall, P. Flicek, D. T. Odom.
“Waves of retrotransposon expansion remodel genome organization and CTCF binding in multiple mammalian lineages,” Cell 148 (2012) 1-12.

C. Kutter, G. Brown, A. Goncalves, S. Watt, M. Wilson, A. Brazma, R. White, D. T. Odom.
“Pol III binding in six mammalian genomes shows high conservation among amino acid isotypes, despite divergence in tRNA gene usage,” Nature Genetics 43 (2011) 948-955.

D. Schmidt, M. Wilson, B. Ballester, P. C. Schwalie, G. Brown, A. Marshall, C. Kutter, S. Watt, C. Martinez-Jimenez, S. Mackay, I. Talianidis, P. Flicek, D. T. Odom.
“Five vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding,” Science 328 (2010) 1036-1040.

Work address: 

Cancer Research UK Cambridge Institute
University of Cambridge
Li Ka Shing Centre
Robinson Way
Cambridge CB2 0RE

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