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ISMB/ECCB
PT41: Shai Lubliner - Modeling Interactions between Adjacent Nucleosomes Improves Genome-wide Predictions of Nucleosome Occupancy
Nucleosome position affects transcriptional regulation, models for position are required for understanding of TR. - Roland Krause
75-90% of the DNA is associated with nucleosomes, play an important regulatory role. - Oliver Hofmann
Use a recently published model to produce the affinity landscape, showing the suitability of nucleosome occupancy. - Roland Krause
Genomic nuceosome affinity landscape based on a thermodynamical model - Oliver Hofmann
The model is probably published here (http://www.ncbi.nlm.nih.gov/pubmed...) - Roland Krause
Can interactions between nucleosomes introduced into the model? - Roland Krause
Two kinds of interactions: direct or bridged by transcription factors or other proteins. - Roland Krause
Additional interactions are important for chromatin organization. DNA bending proteins, TF, histone modifications, etc. - Oliver Hofmann
First approach focuses on direct interaction, including the distance between the nucleosomes. - Roland Krause
Trying to capture interactions between adjacent nucleosomes (cooperative effects) - Oliver Hofmann
What types of functions can represent cooperativity types? - Roland Krause
Notable features include a right shifted main peak, followed by exponential decay. - Roland Krause
Tested Exponential, Stepped Exp, S-ES, Stepping-Off and Stepping-On - Roland Krause
Sampled 5000 configurations and compared it to the linker length preference. - Roland Krause
Can the model properly learned? - Roland Krause
Repeat with data samples, add noise and try to fit different models to the sampled occupancy landscape - Oliver Hofmann
Used synthetic data, including experimental noise, then forgot the algorithm to generate the data and used the previously described models. - Roland Krause
Exponential function shows a good correlation in five-fold cross-validation, with the model incorporating the interaction outperforming the ones without. - Roland Krause
Are the interactions relevant in vivo and in vitro? - Roland Krause
For an in vitro validation the Exp, Step functions work better than the no cooperativity model - Oliver Hofmann
Short linker lengths are favored. - Roland Krause
Interactions are also important using in vivo data, data from several chromosomes and different organisms (yeast and C. elegans) show similar results. - Roland Krause
The interesting part -- biological basis for this preference? - Oliver Hofmann
The in vitro system consists of nucleosomes and DNA only. - Roland Krause
shorter length may allow for interaction of nucleosomes, energetically favoring their shift from otherwise better binding positions - Oliver Hofmann
Hypothesis: electrostatic interaction between nucleosomes, which has been described previously but not shown in the data. - Roland Krause
# Surprised that the very model was not presented in the talk. - Roland Krause
# Wonder whether there is a difference between promoters, other nucleosome covered regions (or other genomic subsets); with the role nucleosome displacement plays in regulation I'd expect some shift - Oliver Hofmann
Q: When you started motivating the model, there was a peak at 10 but the sample data did not have that.[?] A: These are effects of histone H1, which are not modeled. There are a lot of question marks about the role of H1 in yeast. The interaction that we modeled are global and can occur anywhere on the DNA. More complex model would incorporate additional local effects, e.g. other factors. - Roland Krause
Q. Have you finished the model for the higher eukaryotes: A The model is independent of the organism. There might be differences, although this is debated. Differnces between yeast and human are known. - Roland Krause