This SuperSeries is composed of the SubSeries listed below.
Integrator regulates transcriptional initiation and pause release following activation.
Disease, Cell line, Treatment
View SamplesWe investigated the genomic occupancy of INTS11, in normal condition and after stimulation of EGF. Total RNAPII was profiled in the presence or absence of INTS11, along with the Super Elongation Complex proteins AFF4 and ELL2. Additionally, we extensively examined the transcriptional response to EGF, before and after depletion of INTS11, using RNA-seq on ribosome-depleted total RNA and Global Run-on sequencing (GRO-seq).
Integrator regulates transcriptional initiation and pause release following activation.
Cell line, Treatment
View SamplesWe report the total RNA-seq results after CDK9, CDK12 and CDK13 depletion in human HCT116 cells for three days. RNA-seq was performed in cells using two non-targeting replicates and two different shRNAs for each CDK knockdown. For each CDK knockdown, most of the differentially expressed genes were down-regulated with a very small subset of genes upregulated. Different CDK proteins control distinct subsets of genes in vivo, with CDK12 and CDK13 sharing more overlap in function compared to CDK9. Besides, CDK12 and CDK13 loss preferentially affects DNA damage response and snRNA gene expression, respectively. Overall design: Examine the changes of mRNA expression levels after CDK9, CDK12 and CDK13 depletion.
Characterization of human cyclin-dependent kinase 12 (CDK12) and CDK13 complexes in C-terminal domain phosphorylation, gene transcription, and RNA processing.
No sample metadata fields
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
Specimen part, Cell line, Treatment
View SamplesMurine ES cell gene expression before RA induction are used to compare gene expression for time-points of 2, 4, 6hrs post-induction.
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
No sample metadata fields
View SamplesDot1 is a methyl transferase that has been shown through a reporter gene to be involved in position effect variegation of gene expression in heterochrmatic regions such as telomeres and the mating type loci in yeast. This study examines the effect of mutation of DOT1 and two other proteins involved in H3K79 methylation, SWI4 and ARD1, on gene expression relative to wt cells.
Dot1 and histone H3K79 methylation in natural telomeric and HM silencing.
No sample metadata fields
View SamplesTranscriptional regulation of developmentally controlled genes is at the heart of differentiation and organogenesis. In this study, we have performed mRNA transcript abdundance analyses in human cells in response to serum activation signal by RNA-seq. Overall design: mRNA transcript abundance determined before and after serum activation signals using two biological replicates.
Dynamic transcriptional events in embryonic stem cells mediated by the super elongation complex (SEC).
No sample metadata fields
View SamplesHistone H3 lysine27-to-methionine (H3K27M) gain-of-function mutations occur in highly aggressive pediatric gliomas. Here, we establish a Drosophila animal model for the pathogenic histone H3K27M mutation and show that its overexpression resembles Polycomb repressive complex 2 (PRC2) loss-of-function phenotypes, causing de-repression of PRC2 target genes and developmental perturbations. Similarly, a H3K9M mutant depletes H3K9 methylation levels and suppresses position-effect variegation in various Drosophila tissues. The histone H3K9 demethylase KDM3B/JHDM2 associates with H3K9M nucleosomes and its overexpression in Drosophila results in loss of H3K9 methylation levels and heterochromatic silencing defects. Here we establish histone lysine-to-methionine mutants as robust in vivo tools for inhibiting methylation pathways that also function as biochemical reagents for capturing site-specific histone-modifying enzymes, thus providing molecular insight into chromatin-signaling pathways. Overall design: RNA-seq of wing imaginal discs expressing either H3.3WT-FLAG-HA or H3.3K27M-FLAG-HA.
Histone H3 lysine-to-methionine mutants as a paradigm to study chromatin signaling.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Specimen part
View SamplesJarid2 was recently identified as an important component of the mammalian Polycomb Repressive Complex 2 (PRC2), where it has a major effect on PRC2 recruitment in mouse embryonic stem cells. Although Jarid2 is conserved in Drosophila, it has not previously been implicated in Polycomb (Pc) regulation. Therefore, we purified Drosophila Jarid2 and its associated proteins and find that Jarid2 associates with all of the known canonical PRC2 components, demonstrating a conserved physical interaction with PRC2 in flies and mammals. Furthermore, in vivo studies with Jarid2 mutants in flies demonstrate that among several histone modifications tested, only H3K27 methylation, the mark implemented by PRC2, was affected. Genome-wide profiling of Jarid2, Su(z)12 and H3K27me3 occupancy by ChIP-seq indicates that Jarid2 and Su(z)12 have a very similar distribution pattern on chromatin. However, Jarid2 and Su(z)12 occupancy levels at some genes are significantly different with Jarid2 being present at relatively low levels at many Pc response elements (PREs) of certain Homeobox (Hox) genes, providing a rationale for why Jarid2 was never identified in Pc screens. Gene expression analyses show that Jarid2 and E(z) (a canonical PRC2 component) are required not only for transcriptional repression but might also function in active transcription. Identification of Jarid2 as a conserved PRC2 interactor in flies provides an opportunity to begin to probe some of its novel functions in Drosophila development.
Polycomb repressive complex 2-dependent and -independent functions of Jarid2 in transcriptional regulation in Drosophila.
Specimen part
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