Linked Life Data

20460467

Source:http://linkedlifedata.com/resource/pubmed/id/20460467

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
17
pubmed:dateCreated
2010-9-22
pubmed:abstractText
The Nrf2 (nuclear factor E2 p45-related factor 2) transcription factor responds to diverse oxidative and electrophilic environmental stresses by circumventing repression by Keap1, translocating to the nucleus, and activating cytoprotective genes. Nrf2 responses provide protection against chemical carcinogenesis, chronic inflammation, neurodegeneration, emphysema, asthma and sepsis in murine models. Nrf2 regulates the expression of a plethora of genes that detoxify oxidants and electrophiles and repair or remove damaged macromolecules, such as through proteasomal processing. However, many direct targets of Nrf2 remain undefined. Here, mouse embryonic fibroblasts (MEF) with either constitutive nuclear accumulation (Keap1(-/-)) or depletion (Nrf2(-/-)) of Nrf2 were utilized to perform chromatin-immunoprecipitation with parallel sequencing (ChIP-Seq) and global transcription profiling. This unique Nrf2 ChIP-Seq dataset is highly enriched for Nrf2-binding motifs. Integrating ChIP-Seq and microarray analyses, we identified 645 basal and 654 inducible direct targets of Nrf2, with 244 genes at the intersection. Modulated pathways in stress response and cell proliferation distinguish the inducible and basal programs. Results were confirmed in an in vivo stress model of cigarette smoke-exposed mice. This study reveals global circuitry of the Nrf2 stress response emphasizing Nrf2 as a central node in cell survival response.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1362-4962
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
38
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
5718-34
pubmed:dateRevised
2011-8-24
pubmed:meshHeading
pubmed-meshheading:20460467-Animals, pubmed-meshheading:20460467-Antioxidants, pubmed-meshheading:20460467-Binding Sites, pubmed-meshheading:20460467-Cell Cycle, pubmed-meshheading:20460467-Cell Proliferation, pubmed-meshheading:20460467-Cell Survival, pubmed-meshheading:20460467-Chromatin Immunoprecipitation, pubmed-meshheading:20460467-Gene Expression Profiling, pubmed-meshheading:20460467-Gene Regulatory Networks, pubmed-meshheading:20460467-Male, pubmed-meshheading:20460467-Mice, pubmed-meshheading:20460467-Mice, Knockout, pubmed-meshheading:20460467-NF-E2-Related Factor 2, pubmed-meshheading:20460467-Oligonucleotide Array Sequence Analysis, pubmed-meshheading:20460467-Regulatory Elements, Transcriptional, pubmed-meshheading:20460467-Sequence Analysis, DNA, pubmed-meshheading:20460467-Transcription, Genetic, pubmed-meshheading:20460467-Xenobiotics
pubmed:year
2010
pubmed:articleTitle
Global mapping of binding sites for Nrf2 identifies novel targets in cell survival response through ChIP-Seq profiling and network analysis.
pubmed:affiliation
Department of Environmental Health Sciences Department, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural