Identification and characterization of cell type-specific and ubiquitous chromatin regulatory structures in the human genome

• Published in: PLoS genetics Vol. 3; no. 8; p. e136
• Main Authors: Xi, Hualin, Shulha, Hennady P, Lin, Jane M, Vales, Teresa R, Fu, Yutao, Bodine, David M, McKay, Ronald D G, Chenoweth, Josh G, Tesar, Paul J, Furey, Terrence S, Ren, Bing, Weng, Zhiping, Crawford, Gregory E
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.08.2007; Public Library of Science (PLoS)
• Subjects: Base Sequence; Binding Sites; CCCTC-Binding Factor; Cell Lineage - genetics; Cells; Cells, Cultured; Chromatin; Chromatin - chemistry; Chromosome Mapping; Cluster Analysis; CpG Islands - genetics; Deoxyribonuclease I - metabolism; DNA-Binding Proteins - metabolism; Gene expression; Genetic aspects; Genetics; Genetics and Genomics; Genome, Human; Genomes; HeLa Cells; Homo (Human); Human genome; Humans; Insulator Elements - genetics; K562 Cells; Microarray Analysis; Molecular Sequence Data; Organ Specificity - genetics; Proteins; Regulatory Elements, Transcriptional; Repressor Proteins - metabolism; Research Design; Sequence Analysis, DNA - methods; United States
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.0030136

The identification of regulatory elements from different cell types is necessary for understanding the mechanisms controlling cell type-specific and housekeeping gene expression. Mapping DNaseI hypersensitive (HS) sites is an accurate method for identifying the location of functional regulatory elements. We used a high throughput method called DNase-chip to identify 3,904 DNaseI HS sites from six cell types across 1% of the human genome. A significant number (22%) of DNaseI HS sites from each cell type are ubiquitously present among all cell types studied. Surprisingly, nearly all of these ubiquitous DNaseI HS sites correspond to either promoters or insulator elements: 86% of them are located near annotated transcription start sites and 10% are bound by CTCF, a protein with known enhancer-blocking insulator activity. We also identified a large number of DNaseI HS sites that are cell type specific (only present in one cell type); these regions are enriched for enhancer elements and correlate with cell type-specific gene expression as well as cell type-specific histone modifications. Finally, we found that approximately 8% of the genome overlaps a DNaseI HS site in at least one the six cell lines studied, indicating that a significant percentage of the genome is potentially functional.