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The nucleosome map of the mammalian liver

Nature Structural & Molecular Biology volume 18, pages 742746 (2011) | Download Citation

Abstract

Binding to nucleosomal DNA is critical for 'pioneer' transcription factors such as the winged-helix transcription factors Foxa1 and Foxa2 to regulate chromatin structure and gene activation. Here we report the genome-wide map of nucleosome positions in the mouse liver, with emphasis on transcriptional start sites, CpG islands, Foxa2 binding sites and their correlation with gene expression. Despite the heterogeneity of liver tissue, we could clearly discern the nucleosome pattern of the predominant liver cell, the hepatocyte. By analyzing nucleosome occupancy and the distributions of heterochromatin protein 1 (Hp1), CBP (also known as Crebbp) and p300 (Ep300) in Foxa1- and Foxa2-deficient livers, we find that the maintenance of nucleosome position and chromatin structure surrounding Foxa2 binding sites is independent of Foxa1 and Foxa2.

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Acknowledgements

We thank A. Fox, O. Smirnova, K. Brondell, A. Chen, A. Riblett and J. LaRossa (University of Pennsylvania) for excellent technical support. This study was supported by the US National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) (P01-DK049210 to K.H.K.). Z.L. was supported by National Sciences and Engineering Research Council of Canada and Juvenile Diabetes Research Foundation postdoctoral fellowship awards. We would like to acknowledge support of the Institute for Diabetes, Obesity, and Metabolism Functional Genomics Core by an NIDDK Research Center grant (P30DK19525).

Author information

Affiliations

  1. Department of Genetics, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Zhaoyu Li
    • , Jonathan Schug
    • , Geetu Tuteja
    • , Peter White
    •  & Klaus H Kaestner
  2. Institute of Diabetes, Obesity and Metabolism, School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.

    • Zhaoyu Li
    • , Jonathan Schug
    • , Geetu Tuteja
    • , Peter White
    •  & Klaus H Kaestner

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Contributions

Z.L. did the majority of experiments and computational analyses. J.S., P.W. and G.T. did a part of the experiments and computational analyses. K.H.K. directed the whole study. Z.L. and K.H.K. designed the experiments and wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Klaus H Kaestner.

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DOI

https://doi.org/10.1038/nsmb.2060

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