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Series GSE23619 Query DataSets for GSE23619
Status Public on Jan 01, 2011
Title Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes (Illumina sequencing data)
Organism Mus musculus
Experiment type Expression profiling by high throughput sequencing
Genome binding/occupancy profiling by high throughput sequencing
Summary Precise control of the innate immune response is required for resistance to microbial infections and maintenance of normal tissue homeostasis. Because this response involves coordinate regulation of hundreds of genes, it provides a powerful biological system to elucidate the molecular strategies that underlie signal- and time-dependent transitions of gene expression. Using a combination of genome-wide and gene-specific approaches, we provide evidence that rather than representing off/on transitions, Toll-like receptor 4 (TLR4)-dependent activation of nearly all immediate/early (I/E) and late response genes results from a sequential process in which signal-independent factors, exemplified by Gabpa, initially establish basal levels of gene expression that are then amplified by signal-dependent transcription factors. Promoters of I/E genes are distinguished from those of late genes by the use of distinct sets of signal-dependent transcription factors, preferential binding of TBP and basal enrichment for RNA Pol II immediately downstream of transcriptional start sites. Global nuclear run-on (GRO) sequencing and total RNA sequencing further indicates that TLR4 signaling markedly increases efficiency of transcriptional elongation of nearly all I/E genes, while RNA splicing is largely unaffected. NCoR/SMRT co-repressor complexes are unexpectedly found to be associated with H3K4me3-positive promoters of TLR4-responsive genes that exhibit a broad range of basal expression levels, implying a dynamic, rather than static role in regulation of gene expression. Collectively, these findings reveal mechanisms underlying temporally distinct patterns of TLR4-dependent gene activation required for homeostasis and effective immune responses.
Overall design ChIP-Seq, Total RNA-Seq, Gro-Seq, and gene expression profiling was performed in macrophages treated with Kdo2 Lipid A. Control samples for H3K4me3 in Macrophages and B cells, in addition to control microarray data are included in GEO accession# GSE21512. FASTA files are available for older experiments that lack quality read information (i.e. no FASTQ file)
Contributor(s) Escoubet-Lozach L, Benner C, Kaikkonen MU, Lozach J, Heinz S, Spann N, Crotti A, Stender J, Ghisletti S, Glass CK
Citation(s) 22174696
Submission date Aug 13, 2010
Last update date May 15, 2019
Contact name Christopher Benner
Organization name University of California, San Diego (UCSD)
Department Medicine
Street address 9500 Gilman Dr. MC 0640
City La Jolla
State/province California
ZIP/Postal code 92093-0640
Country USA
Platforms (2)
GPL9185 Illumina Genome Analyzer (Mus musculus)
GPL9250 Illumina Genome Analyzer II (Mus musculus)
Samples (23)
GSM537987 ThioMac-H3K4me3-ChIP-Seq
GSM537988 ThioMac-input-ChIP-Seq
GSM537992 Bcell-H3K4me3-ChIP-Seq
This SubSeries is part of SuperSeries:
GSE23622 Mechanisms Establishing TLR4-Responsive Activation States of Inflammatory Response Genes
SRA SRP003475
BioProject PRJNA133349

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Supplementary file Size Download File type/resource
GSE23619_RAW.tar 4.1 Gb (http)(custom) TAR (of BED, FA, TXT)
SRA Run SelectorHelp
Processed data provided as supplementary file
Raw data are available in SRA

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