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Mus musculus
11 Downloadable Samples
Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 7 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st), Illumina Genome Analyzer II
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
The peroxisome proliferator-activated receptor co-activator 1 (PGC-1) coordinates the transcriptional network response to promote an improved endurance capacity in skeletal muscle, e.g. by co-activating the estrogen-related receptor (ERR) in the regulation of oxidative substrate metabolism. Despite a close functional relationship, the interaction between these two proteins has not been studied on a genomic level. We now mapped the genome-wide binding of ERR to DNA in skeletal muscle cell line with elevated PGC-1 and linked the DNA recruitment to global PGC-1 target gene regulation. We found that, surprisingly, ERR co-activation by PGC-1 is only observed in the minority of all PGC-1 recruitment sites. Nevertheless, a majority of PGC-1 target gene expression is dependent on ERR. Intriguingly, the interaction between these two proteins is controlled by the genomic context of response elements, in particular the relative GC and CpG content, monomeric and dimeric repeat binding site configuration for ERR, and adjacent recruitment of the transcription factor SP1. These findings thus not only reveal an unprecedented insight into the regulatory network underlying muscle cell plasticity, but also strongly link the genomic context of DNA response elements to control transcription factor - co-regulator interactions.
Publication Title
The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
- Illumina Genome Analyzer II, Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Skeletal muscle tissue shows an extraordinary cellular plasticity, but the underlying molecular mechanisms are still poorly understood. Here we use a combination of experimental and computational approaches to unravel the complex transcriptional network of muscle cell plasticity centered on the peroxisome proliferator-activated receptor coactivator 1 (PGC-1), a regulatory nexus in endurance training adaptation. By integrating data on genome-wide binding of PGC-1 and gene expression upon PGC-1 over-expression with comprehensive computational prediction of transcription factor binding sites (TFBSs), we uncover a hitherto underestimated number of transcription factor partners involved in mediating PGC-1 action. In particular, principal component analysis of TFBSs at PGC-1 binding regions predicts that, besides the well-known role of the estrogen-related receptor (ERR), the activator protein-1 complex (AP-1) plays a major role in regulating the PGC-1-controlled gene program of hypoxia response. Our findings thus reveal the complex transcriptional network of muscle cell plasticity controlled by PGC-1.
Publication Title
Transcriptional network analysis in muscle reveals AP-1 as a partner of PGC-1α in the regulation of the hypoxic gene program.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 9 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
The Genomic Context and Corecruitment of SP1 Affect ERRα Coactivation by PGC-1α in Muscle Cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 20 Downloadable Samples
- Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
In the present study we have studied the mechanistic and functional aspects of NCoR1 function in mouse skeletal muscle. NCoR1 muscle-specific knockout mice exhibited an increased oxidative metabolism. Global gene expression analysis revealed a high overlap between the effects of NCoR1 deletion and peroxisome proliferator-activated receptor (PPAR) gamma coactivator 1alpha (PGC-1alpha) overexpression on oxidative metabolism in skeletal muscle. The repressive effect of NCoR1 on oxidative phosphorylation gene expression specifically antagonizes PGC-1alpha-mediated coactivation of ERRalpha. We therefore delineated the molecular mechanism by which a transcriptional network controlled by corepressor and coactivator proteins determines the metabolic properties of skeletal muscle, thus representing a potential therapeutic target for metabolic diseases.
Publication Title
The corepressor NCoR1 antagonizes PGC-1α and estrogen-related receptor α in the regulation of skeletal muscle function and oxidative metabolism.
Sample Metadata Fields
Sex, Disease
View Samples- Homo sapiens
- 2 Downloadable Samples
- IlluminaHiSeq2500
Description
The inflammatory gene response requires activation of the protein kinase TAK1, but it is currently unknown how TAK1-derived signals coordinate transcriptional programs in the genome. We determined the genome-wide binding of the TAK1-controlled NF-?B subunit p65 in relation to active enhancers and promoters of transcribed genes by ChIP-seq experiments. Out of 35,000 active enhancer regions, 410 H3K4me1-positive enhancers show interleukin (IL)-1-induced H3K27ac and p65 binding. Inhibition of TAK1, IKK2 or depletion of p65 blocked inducible enhancer activation and gene expression. As exemplified by the CXC chemokine cluster located on chromosome 4, the TAK1-p65 pathway also regulates the recruitment kinetics of the histone acetyltransferase CBP, of NF-?B p50 and of AP-1 transcription factors to both, promoters and enhancers. This study provides a high resolution view of epigenetic changes occurring during the IL-1 response and allows the first genome-wide identification of a novel class of inducible p65 NF-?B-dependent enhancers in epithelial cells. Overall design: RNA-seq of KB cells either untreated or treated with IL-1 alpha
Publication Title
The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.
Sample Metadata Fields
No sample metadata fields
View Samples
GSE22176- Homo sapiens
- 78 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 54 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples- Homo sapiens
- 24 Downloadable Samples
- Affymetrix Human Gene 1.0 ST Array (hugene10st)
Description
Genome-wide expression analysis of hapmap lymphoblastoid and ENCODE project cell lines stimulated with calcitriol and/or estrogen
Publication Title
A ChIP-seq defined genome-wide map of vitamin D receptor binding: associations with disease and evolution.
Sample Metadata Fields
Cell line, Time
View Samples