Abstract
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.
Highlights
The positioning of nucleosomes along eukaryotic chromatin affects accessibility of the genomic DNA in vivo
We report that the CCCTC-binding factor (CTCF), a protein that binds insulator elements to prevent the spreading of heterochromatin and restricting transcriptional enhancers from activating unrelated promoters, possesses greater ability to position nucleosomes across the human genome than does the transcription start site (TSS)
The nucleosomes enriched in the histone modifications previously implicated to correlate with active transcription tend to have less protected DNA against digestion by micrococcal nuclease, or greater DNA accessibility
Summary
The positioning of nucleosomes along eukaryotic chromatin affects accessibility of the genomic DNA in vivo. Nucleosomes may bind to some genomic regions tightly and prevent transcription factors from approaching their sites. Strategically positioned nucleosomes can promote long-range DNA bending and allow distal enhancers to interact with the transcriptional machinery [1,2,3]. Crystal structures show that each nucleosome contains 147 base-pairs (bp) of DNA tightly wrapped around an octamer of H2A, H2B, H3 and H4 histone proteins [4]. The linker DNA between two neighboring nucleosomes is ,20 bp in Saccharomyces cerevisiae [5] and estimated to be 70 bp in higher eukaryotes [6]. Defined lysine and arginine residues in histone tails are often methylated and/or acetylated, which can recruit chromatin remodeling factors and regulate transcription. Histone variants prefer selected genomic regions, e.g. H2A.Z tends to flank nucleosome-free regions [7,8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
