UMMS Affiliation

Department of Biochemistry and Molecular Pharmacology; Program in Bioinformatics and Integrative Biology; Program in Molecular Medicine



Document Type


Medical Subject Headings

Binding Sites; Chromatin Assembly and Disassembly; DNA-Binding Proteins; *Genome, Human; Histones; Humans; Micrococcal Nuclease; Nucleosomes; Repressor Proteins; Transcription Factors


Bioinformatics | Computational Biology | Genetics and Genomics | Systems Biology


Chromatin structure plays an important role in modulating the accessibility of genomic DNA to regulatory proteins in eukaryotic cells. We performed an integrative analysis on dozens of recent datasets generated by deep-sequencing and high-density tiling arrays, and we discovered an array of well-positioned nucleosomes flanking sites occupied by the insulator binding protein CTCF across the human genome. These nucleosomes are highly enriched for the histone variant H2A.Z and 11 histone modifications. The distances between the center positions of the neighboring nucleosomes are largely invariant, and we estimate them to be 185 bp on average. Surprisingly, subsets of nucleosomes that are enriched in different histone modifications vary greatly in the lengths of DNA protected from micrococcal nuclease cleavage (106-164 bp). The nucleosomes enriched in those histone modifications previously implicated to be correlated with active transcription tend to contain less protected DNA, indicating that these modifications are correlated with greater DNA accessibility. Another striking result obtained from our analysis is that nucleosomes flanking CTCF sites are much better positioned than those downstream of transcription start sites, the only genomic feature previously known to position nucleosomes genome-wide. This nucleosome-positioning phenomenon is not observed for other transcriptional factors for which we had genome-wide binding data. We suggest that binding of CTCF provides an anchor point for positioning nucleosomes, and chromatin remodeling is an important component of CTCF function.


Citation: PLoS Genet. 2008 Jul 25;4(7):e1000138. doi: 10.1371/journal.pgen.1000138. Link to article on publisher's site

Copyright: © 2008 Fu et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Related Resources

Link to Article in PubMed



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