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

  1. Michael Y Tolstorukov1,
  2. Peter V Kharchenko1,
  3. Joseph A Goldman2,
  4. Robert E Kingston2 and
  5. Peter J Park1,3
  1. 1 Harvard Medical School;
  2. 2 Massachusetts General Hospital

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 tri-methylated 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 about 120-bp of DNA from MNase digestion and exhibit specific sequence preferences, suggesting a novel mechanism of nucleosome organization for the H2A.Z variant.

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Footnotes

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

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