80% of the genomic binding sites of the histone acetyltransferase Gcn5 are colocalizing with CP190 binding. Depletion of CP190 reduces the number of Gcn5 binding sites and binding strength to chromatin. Binding dependency was further supported by Gcn5 mediated co-precipitation of CP190 Overall design: RNA-seq expression profiles of drosophila S2 mRNA after depletion of CP190 and Gcn5
Chromatin binding of Gcn5 in Drosophila is largely mediated by CP190.
Specimen part, Treatment, Subject
View SamplesActivation of the MLL-ENL-ERtm oncogene initiates aberrant proliferation of myeloid progenitors. Here, we show induction of a fail-safe mechanism mediated by the DNA damage response (DDR) machinery that results in activation of the ATR/ATM-Chk1/Chk2-p53/p21 checkpoint and cellular senescence at early stages of cellular transformation caused by a regulatable MLL-ENL-ERtm in mice. Furthermore, we identified the transcription program underlying this intrinsic anti-cancer barrier, and DDR-induced inflammatory regulators that fine-tune the signaling towards senescence, thereby modulating the fate of MLL-ENL-immortalized cells in a tissue-environment-dependent manner. Our results indicate that DDR is a rate-limiting event for acquisition of stem cell-like properties in MLL-ENL-ERtm-mediated transformation, as experimental inhibition of the barrier accelerated the transition to immature cell states and acute leukemia development.
DNA damage response and inflammatory signaling limit the MLL-ENL-induced leukemogenesis in vivo.
Specimen part, Disease stage
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Choice of binding sites for CTCFL compared to CTCF is driven by chromatin and by sequence preference.
Cell line, Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Specimen part, Cell line
View SamplesThe heterogeneous collection of NuRD complexes can be grouped into the MBD2 or MBD3 containing complexes MBD2-NuRD and MBD3-NuRD. MBD2 is known to bind to methylated CpG sequences in vitro in contrast to MBD3. Although functional differences have been described, a direct comparison of MBD2 and MBD3 in respect to genome-wide binding and function has been lacking. Here we show when depleting cells for MBD2, the MBD2 bound genes increase their activity, whereas MBD2 plus MBD3 bound genes reduce their activity. Most strikingly, MBD3 is enriched at active promoters, whereas MBD2 is bound at methylated promoters and enriched at exon sequences of active genes. This suggests a functional connection between MBD2 binding to chromatin and splicing.
Differential roles for MBD2 and MBD3 at methylated CpG islands, active promoters and binding to exon sequences.
Cell line
View SamplesGene expression is tightly linked to histone acetylation on lysine residues that can be recognized by bromodomains. The testis-specific bromodomain protein tBRD-1 is essential for male fertility and might act as a co-factor of testis-specifc TAFs. Here, we perform microarray analyses and demonstrate that tBRD-1 selectively controls gene expression in male germ cells
tBRD-1 selectively controls gene activity in the Drosophila testis and interacts with two new members of the bromodomain and extra-terminal (BET) family.
Specimen part
View SamplesThe 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
The Activation of IL-1-Induced Enhancers Depends on TAK1 Kinase Activity and NF-κB p65.
No sample metadata fields
View SamplesWhole transcriptome for PRMT6 knock-out and control NT2/D1 cells with and without ATRA (all-trans retinoic acid) was sequenced. These samples were compared to each other to find differentially regulated genes and PRMT6-dependent transcriptome in pluripotency and differentiating cells. Overall design: Examining of PRMT6-dependent transcriptome in NT2/D1 cells using RNAseq.
Genomic Location of PRMT6-Dependent H3R2 Methylation Is Linked to the Transcriptional Outcome of Associated Genes.
Specimen part, Cell line, Subject
View SamplesUnderstanding the physiological relevance of structures in mammalian mRNAs remains elusive, especially considering the global unfolding of mRNA structures in eukaryotic organisms recently examined, as well as the decade-long observation that mRNAs generally seem no more likely than random sequences to be stably folded. Here we show that RNA secondary structures, mostly weak and close-to-random, facilitate the 3'-end processing of thousands of human mRNAs by juxtaposing poly(A) signals (PASs) and cleavage sites that are otherwise too far apart. Folding of these 3'-end structures also enhances mRNA stability. Global structure probing shows that 3'-end regions are indeed folded in cells despite substantial unfolding of PAS-upstream regions. Analyses of thousands of ectopically expressed variants prove that folding both enhances processing and increases stability. Mutagenesis of a genomic locus further implicates structure-controlled processing in regulating neighboring gene expression. These results reveal widespread roles for RNA structure in mammalian mRNA biogenesis and metabolism. Overall design: This series includes 8 samples designed to measure the efficiency of 3'' end processing from a reporter library expressed in HEK293T cells and HeLa cells, in steady state or in nascent RNAs (by 4sU labeling and capture).
Widespread Influence of 3'-End Structures on Mammalian mRNA Processing and Stability.
Cell line, Subject
View SamplesSmall endogenous C. elegans RNAs from L4 and young adult worms were prepared for sequencing using a protocol derived from Batista et al., (2008) and Lau et al. (2001). The small-RNA libraries were constructed using a method that does not require a 5' monophosphate (called 5' monophosphate-independent method, Ambros et al., 2003) to profile secondary siRNAs that have 5' triphosphorylated G. All preprocessed small-RNA reads were mapped to genome (ce6), allowing no mismatches. After excluding miRNAs, 21U RNAs, rRNAs, and other structural ncRNAs, the remaining reads were classified as 22G RNAs, 26G RNAs, and other siRNAs, based on their length and 5' terminal nucleotide. Overall design: Small-RNA libraries were sequenced in L4 and young adult stages in C.elegans.
Long noncoding RNAs in C. elegans.
Cell line, Subject
View Samples