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Vortrag von Prof. Dr. Paul Flicek im Rahmen unserer ZBI "Distinguished Speaker Series"

Am Mittwoch, 14. Dezember 2011 wird Prof. Dr. Paul Flicek (European Bioinformatics Institute, Hinxton, Cambridge, UK) im Rahmen der ZBI "Distinguished Speaker Series" einen Vortrag zum Thema "Insights into vertebrate genome evolution from comparative functional genomics" halten (Raum 001, ZBI (Gebäude E 2.1); Beginn: Punkt 17:00 Uhr)..



Across mammalian evolution, the set of protein coding genes is relatively consistent and tissue-level gene expression and function are largely unchanged.  At the same time, a key component of gene regulation, the binding locations of most transcription factors change rapidly over evolutionary time.  In collaboration with Duncan Odom’s laboratory at the University of Cambridge, we have explored this apparent paradox and the evolutionary dynamics of transcription factor (TF) and transcriptional insulator binding through a series of comparative functional genomics experiments mapping their binding in homologous tissues in multiple vertebrate species.


In all cases, the majority of DNA-protein binding events are specific to given vertebrate lineages and lineage specific repeats play an important role in determining the location of these events.   For most site-specific transcription factors, the fraction of sites that are consistently occupied over evolutionary time is extremely small due to rapid birth and death events driven by genetic drift.  In dramatic contrast, the transcriptional insulator CTCF has a remarkably larger stable core set of binding events, yet shows massive and lineage-specific expansion in its binding via a piggy-back mechanism exploiting SINE elements.  The inclusion of data from species chosen by evolutionary distance suggests both TF and CTCF binding sites decay with a predictable rate, driven both by apparently random changes and retention of important functional binding regions.  However, the full set of functional TF binding regions do not exhibit higher levels of sequence constraint than the set of all binding events, suggesting that improvements to models describing the sequence evolution in these regions is required.


Taken together, our data provides significant insight into the mechanisms of how genomic regulatory networks evolve among mammals.