Comment[ArrayExpressAccession]	E-GEOD-41820
MAGE-TAB Version	1.1			
Public Release Date	2012-10-24
Investigation Title	High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq			
Comment[Submitted Name]	High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq
Experiment Description	The aryl hydrocarbon receptor (AHR) and AHR nuclear translocator (ARNT) activated complex regulates genes in response to the environmental contaminant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). AHR has also emerged as a potential therapeutic target for the treatment of human diseases and different cancers, including breast cancer. To better understand AHR and ARNT signaling in breast cancer cells, we used chromatin immunoprecipitation linked to high throughput sequencing to identify AHR- and ARNT-binding sites across the genome in TCDD treated MCF-7 cells. We identified 2,594 AHR-bound, 1,352 ARNT-bound and 882 high confidence AHR/ARNT co-bound regions. No significant differences in the genomic distribution of AHR and ARNT were observed. Approximately 60% of the co-bound regions contained at least one core AHRE, 5'-GCGTG-3'. AHR/ARNT peak density was the highest within 1 kb of transcription start sites (TSS); however, a number of AHR/ARNT co-bound regions were located as far as 100 kb from TSS. De novo motif discovery identified a symmetrical variation of the AHRE (5'-GTGCGTG-3'), as well as FOXA1 and SP1 binding motifs. Microarray analysis identified 104 TCDD responsive genes where 98 genes were up-regulated by TCDD. Of the 104 regulated genes, 69 (66.3%) were associated with an AHR- or ARNT-bound region within 100 kb of their TSS. Overall our study identified AHR/ARNT co-bound regions across the genome, revealed the importance but not absolute requirement for an AHRE in AHR/ARNT interactions with DNA, and identified a modified AHRE motif, thereby increasing our understanding of AHR/ARNT signaling pathway. Examination of genome-wide AHR and ARNT binding pattern in MCF-7			
Term Source Name	ArrayExpress	EFO
Term Source File	http://www.ebi.ac.uk/arrayexpress/	http://www.ebi.ac.uk/efo/efo.owl		
Person Last Name	Lo	Lo	Matthews	
Person First Name	Raymond	Raymond	Jason	
Person Email	r.lo@mail.utoronto.ca			
Person Affiliation	University of Toronto			
Person Address	Pharmacology, University of Toronto, 1 King's College Circle Rm 4336, Toronto, Ontario, Canada			
Person Roles	submitter			
Protocol Name	P-GSE41820-1	P-GSE41820-3	P-GSE41820-2	P-GSE41820-4
Protocol Description	10 nM dioxin for 45 min	Cell extracts were sonicated and AHR/ARNT-DNA complexes are immunoprecipitated. Immunoprecipitated DNA was amplified using sigma aldrich SeqPlex whole-genome amplification kit. Library was prepared according to Illumina's instruction by BGI (Shenzhen, China).	MCF-7 cells were grown in low glucose DMEM supplemented by steroid-free serum.	Basecalling were performed using CASAVA ChIP-Seq reads were aligned to the human genome version 19 using Short Oligo Analysis Package 2.21 (BGI, Shenzhen, China) (Li et al. 2009). AHR Replicates 1 and 3 were compared against IgG Replicate 1 and 3. ARNT Replicates 1 and 2 were compared against IgG Replicate 1 and 2. Peaks were called using CisGenome v2.0 with the following settings: Read Extension = 150 bp; Bin Size = 50 bp; Max Gap = 50 bp; Min Peak Length = 100 bp Genome_build: hg19 Supplementary_files_format_and_content: BED
Protocol Type	specified_biomaterial_action	nucleic_acid_extraction	grow	feature_extraction
Experimental Factor Name	CHIP ANTIBODY			
Experimental Factor Type	chip antibody			
Publication Title	High-resolution genome-wide mapping of AHR and ARNT binding sites by ChIP-Seq.			
Publication Author List	Lo R, Matthews J			
PubMed ID	22903824			
Publication DOI	10.1093/toxsci/kfs253			
Comment[SecondaryAccession]	GSE41820			
Comment[GEOReleaseDate]	2012-10-24			
Comment[ArrayExpressSubmissionDate]	2012-10-24			
Comment[GEOLastUpdateDate]	2012-10-26			
Comment[AEExperimentType]	ChIP-seq			
Comment[SecondaryAccession]	SRP016797			
Comment[SequenceDataURI]	http://www.ebi.ac.uk/ena/data/view/SRR608880-SRR608887			
SDRF File	E-GEOD-41820.sdrf.txt