User:Odom:Schmidt

Odom laboratory

Home        Members        Research        Pubs        Protocols        Pix        Contact       

Dominic Schmidt

Dominic Schmidt Doctoral Student Darwin College, Department of Oncology, University of Cambridge Cancer Research UK, Cambridge Research Institute Li Ka Shing Centre Robinson Way, Cambridge, CB2 0RE phone: +44-1223404248 email: Dominic.Schmidt 'at' cancer 'dot' org 'dot' uk

Qualifications and Personal History

Education current, Doctoral Student at the University of Cambridge 2007, German Diplom Degree (Biochemistry) at the Max Planck Institute for Molecular Genetics and the Freie Universität Berlin

Research

Research Interests Transcription factors (TFs) direct gene expression by binding to DNA regulatory regions. To explore the evolution of gene regulation, we experimentally determined the genome-wide occupancy of two TFs, CEBPA and HNF4A, in livers of five vertebrates. Although each TF displays highly conserved DNA binding preferences, most binding is species-specific, and aligned binding events present in all five species are rare. Regions near genes with expression levels dependent on a TF are often bound by the TF in multiple species, yet show no enhanced DNA sequence constraint. Binding divergence between species can be largely explained by sequence changes to the bound motifs. Among the binding events lost in one lineage, only half are recovered by another binding event within 10 kilobases. Our results reveal large interspecies differences in transcriptional regulation and provide insight into their evolution: Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD, Marshall A, Kutter C, Watt S, Martinez-Jimenez CP, Mackay S, Talianidis I, Flicek P, and Odom DT. Five-Vertebrate ChIP-seq Reveals the Evolutionary Dynamics of Transcription Factor Binding. Science 2010 Apr 8. doi:10.1126/science.1186176 pmid:20378774. We recently showed that cohesin co-binds across the genome with transcription factors independently of CTCF, plays a functional role in estrogen-regulated transcription, and may help mediate tissue-specific transcriptional responses via long-range chromosomal interactions: Schmidt D, Schwalie PC, Ross-Innes CS, Hurtado A, Brown GD, Carroll JS, Flicek P, and Odom DT. A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res 2010 Mar 10. doi:10.1101/gr.100479.109 pmid:20219941. Myriad points of control influence gene expression; however, it has also been an unresolved question as to which of these mechanisms has the most influence globally. We recently showed that each layer of transcriptional regulation within the adult hepatocyte, from the binding of liver master regulators and chromatin remodelling complexes to the output of the transcriptional machinery, is directed primarily by DNA sequence. Although conservation of motifs alone cannot predict transcription factor binding, we show that within the genetic sequence there must be embedded adequate instructions to direct species-specific transcription: Wilson MD, Barbosa-Morais NL, Schmidt D, Conboy CM, Vanes L, Tybulewicz VL, Fisher EM, Tavare S, and Odom DT. Species-Specific Transcription in Mice Carrying Human Chromosome 21. Science 2008 Sep 11. doi:10.1126/science.1160930 pmid:18787134. We published a detailed protocol for ChIP-seq for whole tissues and cell lines. Furthermore we compared the influence of sequencing depth on peak calling using matched ChIP-chip data from the identical sequencing libraries: Schmidt D, Wilson MD, Spyrou C, Brown GD, Hadfield J, and Odom DT. ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions. Methods 2009 Jul; 48(3) 240-8. doi:10.1016/j.ymeth.2009.03.001 pmid:19275939. Schmidt D, Stark R, Wilson MD, Brown GD, and Odom DT. Genome-scale validation of deep-sequencing libraries. PLoS ONE 2008; 3(11) e3713. doi:10.1371/journal.pone.0003713 pmid:19002256. I received my german diplom degree in Biochemistry at the Max Planck Institute for Molecular Genetics in the department for Vertebrate Genomics of Hans Lehrach in the laboratory of Marie-Laure Yaspo. The focus of my research was the analysis of gene regulatory networks, especially for human chromosome 21 encoded transcription factors. For this purpose I worked with ChIP-chip using high density and developed ChIP-seq using next generation sequencing technology. We published ChIP-seq for RNA-polymerase II in human cells together with RNA-seq: Sultan M, Schulz MH, Richard H, Magen A, Klingenhoff A, Scherf M, Seifert M, Borodina T, Soldatov A, Parkhomchuk D, Schmidt D, O'Keeffe S, Haas S, Vingron M, Lehrach H, and Yaspo ML. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science 2008 Aug 15; 321(5891) 956-60. doi:10.1126/science.1160342 pmid:18599741.

Publications

Schmidt D, Wilson MD, Ballester B, Schwalie PC, Brown GD, Marshall A, Kutter C, Watt S, Martinez-Jimenez CP, Mackay S, Talianidis I, Flicek P, and Odom DT. Five-vertebrate ChIP-seq reveals the evolutionary dynamics of transcription factor binding. Science. 2010 May 21;328(5981):1036-40. DOI:10.1126/science.1186176 | Schmidt D, Schwalie PC, Ross-Innes CS, Hurtado A, Brown GD, Carroll JS, Flicek P, and Odom DT. A CTCF-independent role for cohesin in tissue-specific transcription. Genome Res. 2010 May;20(5):578-88. DOI:10.1101/gr.100479.109 | Ross-Innes CS, Stark R, Holmes KA, Schmidt D, Spyrou C, Russell R, Massie CE, Vowler SL, Eldridge M, and Carroll JS. Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev. 2010 Jan 15;24(2):171-82. DOI:10.1101/gad.552910 | Schmidt D, Wilson MD, Spyrou C, Brown GD, Hadfield J, and Odom DT. ChIP-seq: using high-throughput sequencing to discover protein-DNA interactions. Methods. 2009 Jul;48(3):240-8. DOI:10.1016/j.ymeth.2009.03.001 | Schmidt D, Stark R, Wilson MD, Brown GD, and Odom DT. Genome-scale validation of deep-sequencing libraries. PLoS One. 2008;3(11):e3713. DOI:10.1371/journal.pone.0003713 | Wilson MD, Barbosa-Morais NL, Schmidt D, Conboy CM, Vanes L, Tybulewicz VL, Fisher EM, Tavaré S, and Odom DT. Species-specific transcription in mice carrying human chromosome 21. Science. 2008 Oct 17;322(5900):434-8. DOI:10.1126/science.1160930 | Sultan M, Schulz MH, Richard H, Magen A, Klingenhoff A, Scherf M, Seifert M, Borodina T, Soldatov A, Parkhomchuk D, Schmidt D, O'Keeffe S, Haas S, Vingron M, Lehrach H, and Yaspo ML. A global view of gene activity and alternative splicing by deep sequencing of the human transcriptome. Science. 2008 Aug 15;321(5891):956-60. DOI:10.1126/science.1160342 |

Miscellaneous

Picture Gallerie Carroll-lab Odom-lab Odom_Lab_Jan2009