Project description:This data was generated by ENCODE. If you have questions about the data, contact the submitting laboratory directly (Terry Furey mailto:tsfurey@duke.edu). If you have questions about the Genome Browser track associated with this data, contact ENCODE (mailto:genome@soe.ucsc.edu). These tracks display DNaseI hypersensitivity (HS) evidence as part of the four Open Chromatin track sets. DNaseI is an enzyme that has long been used to map general chromatin accessibility, and DNaseI "hypersensitivity" is a feature of active cis-regulatory sequences. The use of this method has led to the discovery of functional regulatory elements that include promoters, enhancers, silencers, insulators, locus control regions, and novel elements. DNaseI hypersensitivity signifies chromatin accessibility following binding of trans-acting factors in place of a canonical nucleosome. Together with FAIRE and ChIP-seq experiments, these tracks display the locations of active regulatory elements identified as open chromatin in multiple cell types (http://hgwdev.cse.ucsc.edu/cgi-bin/hgEncodeVocab?type=cellType) from the Duke, UNC-Chapel Hill, UT-Austin, and EBI ENCODE group. Within this project, open chromatin was identified using two independent and complementary methods: these DNaseI HS assays and Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE), combined with chromatin immunoprecipitation (ChIP) for select regulatory factors. DNaseI HS and FAIRE provide assay cross-validation with commonly identified regions delineating the highest confidence areas of open chromatin. ChIP assays provide functional validation and preliminary annotation of a subset of open chromatin sites. Each method employed Illumina (formerly Solexa) sequencing by synthesis as the detection platform. The Tier 1 and Tier 2 cell types were additional verified by a second platform, high-resolution 1% ENCODE tiled microarrays supplied by NimbleGen. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

Project description:These tracks display a synthesis of evidence from different assays as part of the four Open Chromatin track sets. This track displays open chromatin regions and/or transcription factor binding sites identified in multiple cell types by one or more complementary methodologies, DNaseI hypersensitivity (HS) (Duke DNaseI HS), Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) (UNC FAIRE), and chromatin immunoprecipitation (ChIP) for select regulatory factors (UTA TFBS). Each methodology was performed on the same cell type using identical growth conditions. (Note: Data for some or all ChIP experiments may not be available for all cell types). Regions that overlap between methodologies identify regulatory elements that are cross-validated indicating high confidence regions. In addition, multiple lines of evidence suggest that regions detected by a single assay (e.g., DNase-only or FAIRE-only) are also biologically relevant (Song et al., submitted). DNaseI HS data: DNaseI is an enzyme that has long been used to map general chromatin accessibility, and DNaseI "hypersensitivity" is a feature of active cis-regulatory sequences.The use of this method has led to the discovery of functional regulatory elements that include promoters, enhancers, silencers, insulators, locus control regions, and novel elements. DNaseI hypersensitivity signifies chromatin accessibility following binding of trans-acting factors in place of a canonical nucleosome. FAIRE data: FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements) is a method to isolate and identify nucleosome-depleted regions of the genome. FAIRE was initially discovered in yeast and subsequently shown to identify active regulatory elements in human cells (Giresi et al., 2007). Similar to DNaseI HS, FAIRE appears to identify functional regulatory elements that include promoters, enhancers, silencers, insulators, locus control regions and novel elements. ChIP data: ChIP (Chromatin Immunoprecipitation) is a method to identify the specific location of proteins that are directly or indirectly bound to genomic DNA. By identifying the binding location of sequence-specific transcription factors, general transcription machinery components, and chromatin factors, ChIP can help in the functional annotation of the open chromatin regions identified by DNaseI HS mapping and FAIRE. Input data: As a background control experiment, we sequenced the input genomic DNA sample that was used for ChIP. Crosslinked chromatin is sheared and the crosslinks are reversed without carrying out the immunoprecipitation step. This sample is otherwise processed in a manner identical to the ChIP sample as described below. The input track is useful in revealing potential artifacts arising from the sequence alignment process such as copy number differences between the reference genome and the sequenced samples, as well as regions of poor sequence alignability. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf

Project description:These tracks display a synthesis of evidence from different assays as part of the four Open Chromatin track sets. This track displays open chromatin regions and/or transcription factor binding sites identified in multiple cell types by one or more complementary methodologies, DNaseI hypersensitivity (HS) (Duke DNaseI HS), Formaldehyde-Assisted Isolation of Regulatory Elements (FAIRE) (UNC FAIRE), and chromatin immunoprecipitation (ChIP) for select regulatory factors (UTA TFBS). Each methodology was performed on the same cell type using identical growth conditions. (Note: Data for some or all ChIP experiments may not be available for all cell types). Regions that overlap between methodologies identify regulatory elements that are cross-validated indicating high confidence regions. In addition, multiple lines of evidence suggest that regions detected by a single assay (e.g., DNase-only or FAIRE-only) are also biologically relevant (Song et al., submitted). DNaseI HS data: DNaseI is an enzyme that has long been used to map general chromatin accessibility, and DNaseI "hypersensitivity" is a feature of active cis-regulatory sequences.The use of this method has led to the discovery of functional regulatory elements that include promoters, enhancers, silencers, insulators, locus control regions, and novel elements. DNaseI hypersensitivity signifies chromatin accessibility following binding of trans-acting factors in place of a canonical nucleosome. FAIRE data: FAIRE (Formaldehyde Assisted Isolation of Regulatory Elements) is a method to isolate and identify nucleosome-depleted regions of the genome. FAIRE was initially discovered in yeast and subsequently shown to identify active regulatory elements in human cells (Giresi et al., 2007). Similar to DNaseI HS, FAIRE appears to identify functional regulatory elements that include promoters, enhancers, silencers, insulators, locus control regions and novel elements. ChIP data: ChIP (Chromatin Immunoprecipitation) is a method to identify the specific location of proteins that are directly or indirectly bound to genomic DNA. By identifying the binding location of sequence-specific transcription factors, general transcription machinery components, and chromatin factors, ChIP can help in the functional annotation of the open chromatin regions identified by DNaseI HS mapping and FAIRE. Input data: As a background control experiment, we sequenced the input genomic DNA sample that was used for ChIP. Crosslinked chromatin is sheared and the crosslinks are reversed without carrying out the immunoprecipitation step. This sample is otherwise processed in a manner identical to the ChIP sample as described below. The input track is useful in revealing potential artifacts arising from the sequence alignment process such as copy number differences between the reference genome and the sequenced samples, as well as regions of poor sequence alignability. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf For each site, the maximum F-Seq Density Signal value has been calculated for each assay that was performed in that cell type. F-Seq employs Parzen kernel density estimation to create base pair scores (Boyle et al., 2008b). Significant regions, or peaks, were determined by fitting the data to a gamma distribution to calculate p-values. Contiguous regions where p-values were below a 0.05 (DNaseI HS, ChIP) or 0.1 (FAIRE) threshold were considered significant. See assay specific description pages ( Duke DNaseI HS, UNC FAIRE and UTA TFBS) for more details. A Fisher's Combined P-value for DNaseI HS and FAIRE was calculated using Fisher's combined probability test. First, a test statistic is calculated using the formula x^2 = -2*sum(ln(pi)) where pi are the p-values calculated for DNaseI HS and FAIRE. X2 follows a chi-squared distribution, thus a combined p-value can be assigned to this test statistic.

Project description:It is generally accepted that exposure to particulate matter (PM) increases the risk of cardiovascular-related morbidity and mortality, though the exact mechanism behind this has yet to be elucidated. Oxidative stress plays a potentially important role in the mechanism of toxicity, with Nrf2 serving as a major antioxidant gene. In the current study, a Nrf2 knockout mouse model was used in combination with an individual ventilated cage (IVC)-based real-ambient PM exposure system to assess the potential cardiotoxicity induced by real-ambient PM exposure and the potential role of Nrf2 and related signaling in this endpoint. After 6- or 11-weeks exposure to PM, ICP-mass spectrometry was used to assess the metal depositions in the heart tissue following PM exposure. Functional and morphological changes in the hearts were investigated with echocardiography and histopathology, and oxidative stress levels were assessed with a serum malondialdehyde content assay. In the further mechanistic study, an RNA-seq technique was utilized to assess the gene transcription status in the hearts of C57/B6 mice exposed to PM with or without Nrf2 knockout. The expression levels of genes of interest were then further investigated with quantitative real-time PCR and western blotting. The results indicated that PM exposure resulted in significant elevation of sodium, potassium, selenium, and ferrum levels in mouse heart tissue. Meanwhile, significantly altered heart function and morphology were observed. Interestingly, Nrf2 knockout led to abolishment of PM-induced effects in several functional parameters but not the morphological changes. Meanwhile, elevated malondialdehyde content was observed in Nrf2 knockout animals. RNA-seq results revealed thousands of genes altered by PM exposure and/or Nrf2 knockout, and this affected several pathways, such as MAPK, phagosome, calcium signaling, and JAK-STAT. In subsequent molecular studies, enhanced nuclear translocation of Nrf2 was also observed following PM exposure, while the MAPK signaling pathway along with related JAK-STAT and TGF-β1 pathway genes, such as p38MAPK, AKT, TAK1, JAK1, STAT3, GRB2, TGFb1, and SMAD2, were confirmed to be affected by PM exposure and/or Nrf2 knockout. The data suggested that PM may induce cardiotoxicity in C57/B6 mice in which Nrf2 plays both protective and detrimental roles involving cardiac-related pathways, such as MAPK, JAK-STAT, and TGF-β1.

			Action	DRS
	SRR709452.fastq.gz	Fastqsanger.gz
	SRR709453.fastq.gz	Fastqsanger.gz
	SRR725592.fastq.gz	Fastqsanger.gz
	SRR733089.fastq.gz	Fastqsanger.gz
	SRR733090.fastq.gz	Fastqsanger.gz

Dataset Information

Mus musculus strain:C57/B6

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