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High-throughput mapping of the chromatin structure of human promoters

Nature Biotechnology volume 25, pages 244–248 (2007)Cite this article

Abstract

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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Figure 1: Positioned nucleosomes are detected in a reproducible manner and identified positioned-nucleosomes correlate well with the literature.
Figure 2: Nucleosome-free regions at transcription start sites of expressed genes or genes with preinitiation complexes (PIC) at their promoters.
Figure 3: MITF binding sites are mostly nucleosome-free.
Figure 4: Variations in nucleosome positioning at the CDK2-SILV promoter locus correlate with lineage-specific SILV expression patterns, because the SILV gene is expressed selectively in melanocytes and melanomas23.

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Acknowledgements

We thank H. Widlund, E. Feige, V. Igras, I. Davis, W. Li and C. Meyer for helpful discussions and support. This work was supported by a grant from the US National Institutes of Health to D.E.F. and the Claudia Adams Barr Award for Innovative Basic Cancer Research to X.S.L. D.E.F. is Distinguished Clinical Scholar of the Doris Duke Charitable Foundation, and Charles and Jan Nirenberg Fellow in Pediatric Oncology at Dana-Farber Cancer Institute. J.S.S. was supported by the Claudia Adams Barr Award from Dana Farber Cancer Institute.

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Author notes

  1. Fatih Ozsolak and Jun S Song: These authors contributed equally to this work.

Authors and Affiliations

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

    Fatih Ozsolak & David E Fisher

  2. Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, 44 Binney Street, Boston, 02115, Massachusetts, USA

    Jun S Song & X Shirley Liu

  3. Harvard School of Public Health, 677 Huntington Avenue, Boston, 02115, Massachusetts, USA

    Jun S Song & X Shirley Liu

Authors
  1. Fatih Ozsolak
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Corresponding authors

Correspondence to X Shirley Liu or David E Fisher.

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Supplementary information

Supplementary Table 1

Genes with at least 2 additional positioned nucleosomes present in MCF7 and T47D but not in MEC. (XLS 60 kb)

Supplementary Data (PDF 914 kb)

Supplementary Discussion (PDF 70 kb)

Supplementary Methods (PDF 45 kb)

Supplementary Notes (PDF 28 kb)

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Ozsolak, F., Song, J., Liu, X. et al. High-throughput mapping of the chromatin structure of human promoters. Nat Biotechnol 25, 244–248 (2007). https://doi.org/10.1038/nbt1279

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