Book of Abstracts: Albany 2009

category image Albany 2009
Conversation 16
June 16-20 2009
© Adenine Press (2008)

Comparative Analysis of Nucleosome Sequence Organization in Human and Yeast Genomes

Eukaryotic DNA is tightly wrapped around a histone protein core constituting the fundamental repeating units of chromatin. The affinity of the histones 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.

We have developed computational methods to detect stable nucleosome positions from the data obtained with high-throughput DNA sequencing combined with chromatin immunoprecipitation. These methods were applied to determine positions of nucleosomes containing the H2A.Z histone variant, histone H3 tri-methylated at lysine 4 (H3K4me3), and nucleosomes not selected for any specific histone variant or modification in human CD4+ T cells.

We observe characteristic patterns of nucleosome distribution around transcription starts of human genes and compare them to the patterns reported for the yeast genome. The results of sequence analysis show that the 10-bp periodicity in dinucleotide distributions, which is pronounced in yeast and other organisms, is not a general feature of human nucleosome sequences. The GC-content of the DNA sequences of bulk human nucleosomes is sharply increased compared to the GC-content of the linkers. Calculations of the DNA deformation energy provide rationale for such a sequence organization showing that GC-rich sequences require less energy to wrap around histone core than AT-rich sequences. We also find that human H2A.Z nucleosomes protect shorter DNA fragments from MNase digestion compared with the H3K4me3-enriched nucleosomes and exhibit different sequence preferences, suggesting a novel mechanism of nucleosome organization for the H2A.Z variant.

Michael Y. Tolstorukov1,2
Peter V. Kharchenko1,2,3
Joseph A. Goldman4
Robert E. Kingston4
Peter J. Park1,2,3

1Center for Biomedical Informatics
Harvard Medical School
10 Shattuck St.
Boston, Massachusetts 02115, USA
2Harvard Partners Center for Genetics and Genomics
New Research Building
77 Avenue Louis Pasteur
Boston, MA 02115, USA
3Children?s Hospital Informatics Program
300 Longwood Ave.
Boston, MA 02115, USA
4Department of Molecular Biology
Massachusetts General Hospital
Boston, MA 02114, USA
Phone: (617) 432-7376, (617) 432-7373
Fax: (617) 525-4488
Email: tolstorukov@gmail.com