Towards Computational Structural Epigenetics at DNA/RNA Levels
Epigenetics, which is the study of changes in gene expression caused by
mechanisms that preserve the underlying DNA sequence, has been an emerging
field of research due to its promises to deliver novel treatments to
genetic diseases. One of the major DNA level epigenetic changes, DNA
methylation is expected to effect nucleosome positioning or chromatin
structure, both influencing gene expression through controlling the
accessibility of transcription on all DNA regions. Due to their
dependence on sequence and/or structural libraries and coarse-grained
modeling, the most successful computational methods for nucleosome
occupancy lack the necessary physics based scaling and resolution to model
delicate epigenetic changes such as DNA methylation. The complex
repertoire of post-transcriptional regulation is dominated with changes
arising at the RNA level. Such changes are but not limited to mRNA
transport or RNA inference both involve large RNA structural assemblies
rich in molecular junctions of various orders. Modeling the role and
epigenetic function of these large RNA complexes is dependent upon
fundamentally novel meso-scale all-atom resolution simulation
technologies. In answer to this need, we present meso-scale all-atom
simulation protocols to predict nucleosome occupancy along genomic
sequences of kilobase length and sample RNA junctions of desired
complexity. The robustness of these methods are demonstrated through
predicting the in vitro experimental occupancy profile for a 20,000 base
pair DNA sequence and the methylation effect on nucleosome occupancy. In
addition, we present applications for sampling RNA junctions and probing
their role in RNA based nanotechnology.
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