Genome-Wide Chromatin Remodeling Identified at GC-Rich Long Nucleosome-Free Regions
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ISMB 2012 Proceedings
To gain deeper insights into principles of cell biology, it is essential to understand how cells reorganize their genomes by chromatin remodeling. We analyzed chromatin remodeling on next generation sequencing data from resting and activated T~cells to determine a whole-genome chromatin remodeling landscape. We consider chromatin remodeling in terms of nucleosome repositioning which can be observed most robustly in long nucleosome-free regions (LNFRs) that are occupied by nucleosomes in another cell state. We found that LNFR sequences are either AT-rich or GC-rich, where nucleosome repositioning was observed much more prominently in GC-rich LNFRs - a considerable proportion of them outside promoter regions. Using support vector machines with string kernels, we identified DNA sequence patterns indicating loci of nucleosome repositioning. GC-rich LNFRs found in resting T~cells showed the most specific and most prominent repositioning patterns. The patterns most indicative for chromatin remodeling are GGGGTGGGG and GGGGCGGGG. The first pattern, GGGGTGGGG is significantly enriched in remodeled LNFRs of resting T cells, regardless of whether these LNFRs are in promoter regions or not. The second pattern, GGGGCGGGG, however, is only indicative for chromatin remodeling outside of promoters. So both patterns hint at hitherto unknown genome-wide mechanisms of chromatin remodeling. Comparisons of the patterns to known binding site patterns suggest the involvement of a Zinc finger protein.