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Series GSE6273 Query DataSets for GSE6273
Status Public on Jan 01, 2007
Title Distinct and predictive chromatin signatures of transcriptional promoters and enhancers in the human genome
Project Pilot ENCODE
Organism Homo sapiens
Experiment type Genome binding/occupancy profiling by genome tiling array
Summary Eukaryotic gene regulatory information is contained within the DNA sequences of cis-regulatory elements and the epigenetic features of the chromatin surrounding these elements. Recent investigations in yeast, fly, and mammalian systems have made significant contributions toward our understanding of the relationship between gene activation and chromatin architecture at transcriptional promoters, but much work remains to improve our knowledge of this relationship at human promoters and other transcriptional regulatory elements, such as enhancers. Here, we report that human promoters and enhancers are associated with distinct chromatin signatures that can be employed to predict these classes of regulatory elements in the human genome. Using a combination of chromatin immunoprecipitation (ChIP) and microarray (ChIP-chip) experiments, we generated high-resolution maps of the chromatin architecture along 30 Mbp of the human genome, located promoters and enhancers in these regions, and characterized the histone modification features of these regulatory elements. We found that active promoters are marked by tri-methylation of histone H3 lysine 4 (H3K4me3) at the transcriptional start site (TSS) and mono-methylation of this residue (H3K4me1) downstream and upstream of the TSS. In contrast, enhancers are marked by H3K4me1 but not H3K4me3. Both types of regulatory elements are also associated with nucleosome depletion and varying degrees of histone acetylation and H3K4me2. We developed computational prediction algorithms that employ the distinct chromatin signatures to identify new promoters and enhancers, predicting over 200 promoters and 400 enhancers within the 30 Mbp regions. This approach correctly predicted over 84% of the regulatory elements identified in an independent, unbiased study of transcription factor binding in the same regions. Our results suggest a histone code for distinct classes of transcriptional regulatory elements, offering insights into the functional relationships between chromatin modifications and regulatory activity in human cells and providing a new resource for the functional annotation of the human genome.
Keywords: ChIP-chip
 
Overall design ChIP-chip analysis was performed to determine the chromatin architecture along 44 human loci selected by the ENCODE consortium as common targets for genomic analysis, totalling 30 Mbp. We investigated the patterns of core histone H3 and five histone modifications: acetylated histone H3 lysine 9/14 (H3ac), acetylated histone H4 lysine 5/8/12/16 (H4ac), and mono-, di-, and tri-methylated histone H3 lysine 4 (H3K4me1, H3K4me2, H3K4me3). We also examined binding of two components of the basal transcriptional machinery (RNAPII and TAF1) and the transcriptional coactivator p300 to identify active promoters and enhancers, respectively. Three biological replicate ChIP-chip experiments were carried out for each marker in HeLa cells before and after treatment with interferon-gamma (IFNγ), as p300 is known to be involved in the cellular response to this cytokine. ChIP samples were amplified, labelled, and hybridized to tiling oligonucleotide microarrays covering the non-repetitive sequences of 30 Mbp at 38-bp resolution.
Web link http://www.ncbi.nlm.nih.gov/projects/geo/info/ENCODE.html
 
Contributor(s) Heintzman ND, Stuart RK, Hon G, Fu Y, Ching CW, Hawkins RD, Barrera LO, Calcar SV, Qu C, Ching KA, Wang W, Weng Z, Green RD, Crawford GE, Ren B
Citation(s) 17277777, 18927605
BioProject PRJNA63415
Submission date Nov 14, 2006
Last update date Jun 28, 2012
Contact name Bing Ren
E-mail(s) biren@ucsd.edu
Organization name Ludwig Institute for Cancer Research
Department Department of Cellular and Molecular Medicine
Lab Laboratory of Gene Regulation
Street address 9500 Gilman Drive
City La Jolla
State/province CA
ZIP/Postal code 92093-0653
Country USA
 
Platforms (3)
GPL1454 RenLab ENCODE PCR tiling array
GPL4558 ENCODE NimbleGen hg16 tiling array
GPL4559 ENCODE NimbleGen hg17 tiling array
Samples (64)
GSM144303 STAT1 IFN-gamma ENCODE NimbleGen hg16 tiling array replicate 1/3
GSM144304 STAT1 IFN-gamma ENCODE NimbleGen hg16 tiling array replicate 2/3
GSM144305 STAT1 IFN-gamma ENCODE NimbleGen hg16 tiling array replicate 3/3

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