Filters
Technology
Platform
SRP045663
Homo sapiens
18 Downloadable Samples
IlluminaHiSeq2000
Description
RNAPII pausing/termination shortly after initiation is a hallmark of gene regulation. However, the molecular mechanisms involved are still to be uncovered. Here, we show that NELF interacts with Integrator complex subunits (INTScom) forming a stable complex with RNPII and Spt5. The interaction between NELF and INTScom subunits is RNA and DNA independent. Using both HIV-1 promoter and genome wide analyses, we demonstrate that Integrator subunits specifically control NELF-mediated RNAPII pause/release at coding genes. The strength of RNAPII pausing is determined by the nature of the NELF-associated complex. Interestingly, in addition to controlling RNAPII pause release INTS11 catalytic subunit of the INTScom is required for the synthesis of full length mRNA. Finally, INTScom-target genes are enriched in HIV-1 TAR/ NELF-binding element and in a 3'box sequence required for snRNA biogenesis. Revealing these unexpected functions of INTScom in regulating RNAPII pausing/release and completion of mRNA synthesis of NELF-target genes will contribute to our understanding of the gene expression cycle. Overall design: Genome-wide expression in HeLa cells in the absence of Integrator 11, or NELF or mock (control) depleted by strand-specific RNASeq (Illumina)
Publication Title
Integrator complex regulates NELF-mediated RNA polymerase II pause/release and processivity at coding genes.
Sample Metadata Fields
No sample metadata fields
View Samples- Drosophila melanogaster
- 5 Downloadable Samples
- Illumina HiSeq 2000
Description
The Drosophila insulator-binding proteins (IBPs) dCTCF/Beaf32 mark the physical borders of chromosomal domains involving co-factors that participate in long-range interactions. Chromosomal borders are further enriched in specific histone modifications yet the implication of histone modifiers and nucleosome dynamics remains largely unknown in such context. Here, we show that IBP depletion impairs nucleosome dynamics over genes flanked by their binding sites. Biochemical purification identifies a key histone methyltransferase of H3K36, NSD/dMes-4, as a novel co-factor of IBPs involved in chromatin accessibility, which specifically co-regulates hundreds of genes flanked by Beaf32/dCTCF. dMes-4 presets chromatin before the recruitment of transcriptional activators including DREF that triggers Set2/Hypb-mediated H3K36me3, RNA splicing and nucleosome positioning. Our results unveil a model for how IBPs regulate gene expression and nucleosome dynamics through NSD/dMes-4, which may contribute to regulate H3K27me3 spreading. Together, our data suggest a division of labor for how IBPs may dynamically regulate chromatin organization depending on distinct co-factors. Overall design: mRNA profiles of Beaf32-depleted or Wild-Type control Drosophila S2 cells by RNASeq (Illumina)
Publication Title
Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes.
Sample Metadata Fields
Cell line, Subject
View Samples- Mus musculus
- 22 Downloadable Samples
Affymetrix Mouse Gene 1.0 ST Array (mogene10st)
Description
Tibialis anterior muscle was damaged by cardiotoxin injection and macrophage subsets were isolated and analyzed by gene expression analysis.
Publication Title
Highly Dynamic Transcriptional Signature of Distinct Macrophage Subsets during Sterile Inflammation, Resolution, and Tissue Repair.
Sample Metadata Fields
Time
View Samples