Comparative analysis of H2A.Z nucleosome organization in the human and yeast genomes

  1. Michael Y. Tolstorukov1,2,5,
  2. Peter V. Kharchenko1,2,3,5,
  3. Joseph A. Goldman4,
  4. Robert E. Kingston4 and
  5. Peter J. Park1,2,3,6
  1. 1 Center for Biomedical Informatics, Harvard Medical School, Boston, Massachusetts 02115, USA;
  2. 2 Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115, USA;
  3. 3 Children's Hospital Informatics Program, Boston, Massachusetts 02115, USA;
  4. 4 Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    1. 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

    • 6 Corresponding author.

      E-mail peter_park{at}harvard.edu; fax (617) 525-4488.

    • [Supplemental material is available online at www.genome.org.]

    • Article published online before print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.084830.108.

      • Received August 12, 2008.
      • Accepted February 22, 2009.
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