Dynamic Regulation of Nucleosome Positioning in the Human Genome. LMI, DIR, NHLBI, NIH

Dustin E. Schones^1,2, Kairong Cui^1,2, Suresh Cuddapah¹, Tae-Young Roh¹, Artem Barski¹, Zhibin Wang¹, Gang Wei¹, and Keji Zhao^1,3

¹ Laboratory of Molecular Immunology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD 20892
² These authors contributed equally to this work.
³ Corresponding author

Summary

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.

Nucleosome Data

Data Set	Tag coordinate bed files	Nucleosome score profiles	UCSC tracks
Resting Nucleosomes	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY
Activated Nucleosomes	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY	chr1 , chr2 , chr3 , chr4 , chr5 , chr6 , chr7 , chr8 , chr9 , chr10 , chr11 , chr12 , chr13 , chr14 , chr15 , chr16 , chr17 , chr18 , chr19 , chr20 , chr21 , chr22 , chrX , chrY

Other Data

Data Set	Tag coordinate bed files	Summay bed file	UCSC track
Resting, Ser5 phosphorylated Pol II	bed file	summary file	custom track
Resting, unphosphorylated Pol II	bed file	summary file	custom track
Activated, Ser5 phosphorylated Pol II	bed file	summary file	custom track
Activated, unphosphorylated Pol II	bed file	summary file	custom track

Information on file formats

Tag coordinate bed files -- contain coordinates for all uniquely mapped reads for each experiment. Each line is in the format:

chromosome

start coordinate

end coordinate

match type

strand

Nucleosome score profiles -- Nucleosome score profiles for given chromosome. For more information see Methods.

Summary bed files -- Bed files displaying the number of uniquely mapped reads in 400 bp windows. All read start coordinates are adjusted by 150 bp in the direction of the strand they map to before summing is done.

UCSC custom tracks -- Automatic linking of summary bed files, or nucleosome score files to the UCSC Genome Browser to create custom tracks.

(Note: all coordinates are from the Human Mar. 2006 (hg18) assembly)

Data corresponding to this project have been deposited in the NCBI Short Read Archive with accession number SRA000234 and the Gene Expression Omnibus with accession number GSE10437