Dynamic Regulation of Nucleosome Positioning in the Human Genome

Dustin E. Schones, Kairong Cui, Suresh Cuddapah, Tae Young Roh, Artem Barski, Zhibin Wang, Gang Wei, Keji Zhao

Research output: Contribution to journalArticlepeer-review

1096 Scopus citations

Abstract

The positioning of nucleosomes with respect to DNA plays an important role in regulating transcription. However, nucleosome mapping has been performed for only limited genomic regions in humans. We have generated genome-wide maps of nucleosome positions in both resting and activated human CD4+ T cells by direct sequencing of nucleosome ends using the Solexa high-throughput sequencing technique. We find that nucleosome phasing relative to the transcription start sites is directly correlated to RNA polymerase II (Pol II) binding. Furthermore, the first nucleosome downstream of a start site exhibits differential positioning in active and silent genes. TCR signaling induces extensive nucleosome reorganization in promoters and enhancers to allow transcriptional activation or repression. Our results suggest that H2A.Z-containing and modified nucleosomes are preferentially lost from the -1 nucleosome position. Our data provide a comprehensive view of the nucleosome landscape and its dynamic regulation in the human genome.

Original languageEnglish
Pages (from-to)887-898
Number of pages12
JournalCell
Volume132
Issue number5
DOIs
StatePublished - 7 Mar 2008

Bibliographical note

Funding Information:
The gene expression analysis using the Affymetrix microarrays was performed by the Gene Expression Core Facility of NHLBI. This work was supported by the Intramural Research Program of the NIH, National Heart, Lung and Blood Institute. We thank Weiqun Peng, Chongzhi Zang, and Raja Jothi for helpful comments and discussions.

Keywords

  • DNA
  • SIGNALING

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