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RESEARCH PAPER
1 Division of Basic Sciences, 2 Division of Public Health Sciences, and 3 Genomics Resource, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA; 4 Department of Radiation Oncology, University of Washington School of Medicine, Seattle, Washington 98195, USA; 5 Department of Biology, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA; 6 Chromatin and Gene Expression Group, Institute for Biomedical Research, University of Birmingham Medical School, Birmingham B152TT, UK; 7 Friedrich Miescher Institute for Biomedical Research, 4058 Basel, Switzerland
The covalent modification of nucleosomal histones has emerged as a major determinant of chromatin structure and gene activity. To understand the interplay between various histone modifications, including acetylation and methylation, we performed a genome-wide chromatin structure analysis in a higher eukaryote. We found a binary pattern of histone modifications among euchromatic genes, with active genes being hyperacetylated for H3 and H4 and hypermethylated at Lys 4 and Lys 79 of H3, and inactive genes being hypomethylated and deacetylated at the same residues. Furthermore, the degree of modification correlates with the level of transcription, and modifications are largely restricted to transcribed regions, suggesting that their regulation is tightly linked to polymerase activity.
[Keywords: Epigenetics; chromatin; histone; Drosophila; chromatin immunoprecipitation; microarray]
Received February 24, 2004; revised version accepted April 14, 2004.
Supplemental material is available at http://www.genesdev.org.
8 Corresponding authors.
E-MAIL dirk{at}fmi.ch; markg{at}fhcrc.org; FAX 41-61-6973976.
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