Laimonas Kelbauskas, The Biodesign Institute, Arizona State University
Nam Chan, Department of Chemistry and Biochemistry, Arizona State University Ralph Bash, The Biodesign Institute, Arizona State University Peter DeBartolo, Department of Chemistry and Biochemistry, Arizona State University Jenny Sun, The Biodesign Institute, Arizona State University Neal Woodbury, The Biodesign Institute, Arizona State University Dennis Lohr, Department of Chemistry and Biochemistry, Arizona State University
Keywords: 5S; FCS; FRET; H2A/H2B; Nucleosome; Sequence-dependent

Gaining access to regulatory DNA sequences buried in nucleosomes is a major impediment to the action of eukaryotic regulatory factors and to the operation of genomic processes. An understanding of how regulators find their target sites and allow transcriptional machinery to access DNA is essential for a fundamental understanding of gene regulation as well as for drug design and new treatments for gene-related diseases. H2A-H2B are released from nucleosomes during the action of several transcription-associated factors; such release enhances the exposure of the remaining histone-bound DNA. We have found that the effect of H2A-H2B release on nucleosomes varies with their DNA sequence; significant, sequence-dependent variations in DNA accessibility between a non-promoter and two promoter nucleosomes were noted in the H2A-H2B depleted complexes. The ability of the DNA sequence itself to contribute significantly to nucleosome stability and DNA accessibility provides a mechanism for differential recognition of specific nucleosomes, such as those on key promoter elements. Significant sequence-dependence nucleosome stability is not widely-recognized but is potentially of fundamental importance to gene expression.

Volume 94, Issue 2, January 15, 2008