Dynamic regulation of nucleosome positioning in the human genome.
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.
Schones
Dustin E
DE
Laboratory of Molecular Immunology, The National Heart, Lung and Blood Institute, NIH, Bethesda, MD 20892, USA.
Cui
Kairong
K
Cuddapah
Suresh
S
Roh
Tae-Young
TY
Barski
Artem
A
Wang
Zhibin
Z
Wei
Gang
G
Zhao
Keji
K
D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D002875:Chromosomes; D004742:Enhancer Elements, Genetic; D015894:Genome, Human; D006657:Histones / Q000378:metabolism; D006801:Humans; D008213:Lymphocyte Activation; D009707:Nucleosomes / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D017422:Sequence Analysis, DNA / Q000379:methods; D024363:Transcription Initiation Site
D006657:Histones; D009707:Nucleosomes; D012319:RNA Polymerase II