Comparative analysis of H2A.Z nucleosome organization in the human and yeast genomes
- Michael Y. Tolstorukov1,2,5,
- Peter V. Kharchenko1,2,3,5,
- Joseph A. Goldman4,
- Robert E. Kingston4 and
- Peter J. Park1,2,3,6
- 1 Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA;
- 2 Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
- 3 Children's Hospital Informatics Program, Boston, Massachusetts 02115, USA;
- 4 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
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↵5 These authors contributed equally to this work.
Abstract
Eukaryotic DNA is wrapped around a histone protein core to constitute the fundamental repeating units of chromatin, the nucleosomes. The affinity of the histone core for DNA depends on the nucleotide sequence; however, it is unclear to what extent DNA sequence determines nucleosome positioning in vivo, and if the same rules of sequence-directed positioning apply to genomes of varying complexity. Using the data generated by high-throughput DNA sequencing combined with chromatin immunoprecipitation, we have identified positions of nucleosomes containing the H2A.Z histone variant and histone H3 trimethylated at lysine 4 in human CD4+ T-cells. We find that the 10-bp periodicity observed in nucleosomal sequences in yeast and other organisms is not pronounced in human nucleosomal sequences. This result was confirmed for a broader set of mononucleosomal fragments that were not selected for any specific histone variant or modification. We also find that human H2A.Z nucleosomes protect only ∼120 bp of DNA from MNase digestion and exhibit specific sequence preferences, suggesting a novel mechanism of nucleosome organization for the H2A.Z variant.
Footnotes
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↵6 Corresponding author.
E-mail peter_park{at}harvard.edu; fax (617) 525-4488.
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[Supplemental material is available online at www.genome.org.]
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Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.084830.108.
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- Received August 12, 2008.
- Accepted February 22, 2009.
- Copyright © 2009 by Cold Spring Harbor Laboratory Press