High-resolution mapping and characterization of open chromatin across the genome.
Mapping DNase I hypersensitive (HS) sites is an accurate method of identifying the location of genetic regulatory elements, including promoters, enhancers, silencers, insulators, and locus control regions. We employed high-throughput sequencing and whole-genome tiled array strategies to identify DNase I HS sites within human primary CD4+ T cells. Combining these two technologies, we have created a comprehensive and accurate genome-wide open chromatin map. Surprisingly, only 16%-21% of the identified 94,925 DNase I HS sites are found in promoters or first exons of known genes, but nearly half of the most open sites are in these regions. In conjunction with expression, motif, and chromatin immunoprecipitation data, we find evidence of cell-type-specific characteristics, including the ability to identify transcription start sites and locations of different chromatin marks utilized in these cells. In addition, and unexpectedly, our analyses have uncovered detailed features of nucleosome structure.
Boyle
Alan P
AP
Institute for Genome Sciences & Policy, Duke University, Durham, NC 27708, USA.
Davis
Sean
S
Shulha
Hennady P
HP
Meltzer
Paul
P
Margulies
Elliott H
EH
Weng
Zhiping
Z
Furey
Terrence S
TS
Crawford
Gregory E
GE
D000465:Algorithms; D019540:Area Under Curve; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000235:genetics*; D047369:Chromatin Immunoprecipitation; D002874:Chromosome Mapping / Q000379:methods; D002877:Chromosomes, Human; D003850:Deoxyribonuclease I / Q000737:chemistry / Q000494:pharmacology; D015894:Genome, Human / Q000235:genetics* / Q000276:immunology; D006657:Histones / Q000737:chemistry; D006801:Humans; D009707:Nucleosomes / Q000737:chemistry; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012372:ROC Curve; D012680:Sensitivity and Specificity; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000378:metabolism
D002843:Chromatin; D006657:Histones; D009707:Nucleosomes; D014157:Transcription Factors; D003850:Deoxyribonuclease I