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Nat Biotechnol. 2007 Feb;25(2):244-8. Epub 2007 Jan 14.

High-throughput mapping of the chromatin structure of human promoters.

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Melanoma Program in Medical Oncology, and Department of Pediatric Oncology, Dana-Farber Cancer Institute, Children's Hospital Boston, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.


Our understanding of how chromatin structure influences cellular processes such as transcription and replication has been limited by a lack of nucleosome-positioning data in human cells. We describe a high-resolution microarray approach combined with an analysis algorithm to examine nucleosome positioning in 3,692 promoters within seven human cell lines. Unlike unexpressed genes without transcription-preinitiation complexes at their promoters, expressed genes or genes containing preinitiation complexes exhibit characteristic nucleosome-free regions at their transcription start sites. The combination of these nucleosome data with chromatin immunoprecipitation-chip analyses reveals that the melanocyte master regulator microphthalmia-associated transcription factor (MITF) predominantly binds nucleosome-free regions, supporting the model that nucleosomes limit sequence accessibility. This study presents a global view of human nucleosome positioning and provides a high-throughput tool for analyzing chromatin structure in development and disease.

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