The NuRD complex is generally thought to repress transcription at both hyper- and hypomethylated regions in the genome. In addition, the complex is involved in the DNA damage response. Here, we show that ZMYND8 bridges NuRD to a number of putative DNA-binding zinc finger proteins. The ZMYND8 MYND domain directly interacts with PPPL? motifs in the NuRD subunit GATAD2A. Furthermore, GATAD2A and GATAD2B exclusively form homodimers and they thus define mutually exclusive NuRD subcomplexes. ZMYND8 and MBD3 share a large number of genome-wide binding sites, mostly active promoters and enhancers. Depletion of ZMYND8 does not affect NuRD occupancy genome-wide and expression of NuRD/ZMYND8 target genes in steady-state asynchronous cells. However, ZMYND8 facilitates immediate recruitment of GATAD2A/NuRD to induced sites of DNA damage. These results thus show that a specific substoichiometric interaction with a NuRD subunit paralogue provides unique functionality to a distinct NuRD subcomplex. Overall design: RNA-seq samples for HeLa FRT-TO mock, ZMYND8KO, and ZMYND8KO-rescue cells
ZMYND8 Co-localizes with NuRD on Target Genes and Regulates Poly(ADP-Ribose)-Dependent Recruitment of GATAD2A/NuRD to Sites of DNA Damage.
Subject
View SamplesDNA repair is an essential cellular process required to maintain genomic stability. Every cell is subjected to thousands of DNA lesions daily under normal changes in transcription. Transcription is a primary process where protein amount and function can be regulated. One aspect of the transcriptional IR response that little is known about on a whole genome basis is alternative transcription. These investigations focus on the response to IR at the exon level in human cells but also at the whole gene level. Whole genome exon arrays were utilized to comprehensively characterize radiation-induced transcriptional expression products in two human cell types, namely EBV-transformed lymphoblast and primary fibroblast cell lines.
DNA repair genes: alternative transcription and gene expression at the exon level in response to the DNA damaging agent, ionizing radiation.
Specimen part, Treatment, Subject
View SamplesHere, we used next-generation RNA sequencing (RNA-seq) to produce a quantitative, whole genome atlas of gene expression for every excitatory neuronal class in the hippocampus; namely, granule cells and mossy cells of the dentate gyrus, and pyramidal cells of areas CA3, CA2, and CA1. Moreover, for the canonical neurons of the trisynaptic loop, we profiled transcriptomes at both dorsal and ventral poles, producing a cell class- and region-specific transcriptional atlas for these canonical populations. Overall design: Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
Hipposeq: a comprehensive RNA-seq database of gene expression in hippocampal principal neurons.
Specimen part, Subject
View SamplesTissue and organ function has been conventionally understood in terms of the interactions among discrete and homogeneous cell types. This approach has proven difficult in neuroscience due to the marked diversity across different neuron classes, but may also be further hampered by prominent within-class variability. Here, we considered a well-defined, canonical neuronal population – hippocampal CA1 pyramidal cells – and systematically examined the extent and spatial rules of transcriptional heterogeneity. Using next-generation RNA sequencing, we identified striking variability in CA1 PCs, such that the differences along the dorsal-ventral axis rivaled differences across distinct pyramidal neuron classes. This variability emerged from a spectrum of continuous expression gradients, producing a profile consistent with a multifarious continuum of cells. This work reveals an unexpected amount of variability within a canonical and narrowly defined neuronal population and suggests that continuous, within-class heterogeneity may be an important feature of neural circuits. Overall design: Hippocampal RNA profiles were generated by deep sequencing on Illumina HiSeq 2500, with three biological replicates per population
Spatial Gene-Expression Gradients Underlie Prominent Heterogeneity of CA1 Pyramidal Neurons.
Subject
View SamplesDupuytren's disease (DD) is a classic example of pathological fibrosis which results in a debilitating disorder affecting a large sector of the human population. It is characterized by excessive local proliferation of fibroblasts and over-production of collagen and other components of the extracellular matrix (ECM) in the palmar fascia. The fibrosis progressively results in contracture of elements between the palmar fascia and skin causing flexion deformity or clawing of the fingers and a severe reduction in hand function. While much is known about the pathogenesis and surgical treatment of DD, little is known about the factors that cause its onset and progression, despite many years of research. Gene expression patterns in DD patients now offers the potential to identify genes that direct the pathogenesis of DD.
Genome-wide analysis using exon arrays demonstrates an important role for expression of extra-cellular matrix, fibrotic control and tissue remodelling genes in Dupuytren's disease.
Specimen part, Disease, Disease stage
View SamplesNeuronal diversity is a defining feature of the mammalian brain deemed necessary for realizing the complex function of the nervous system. In order to begin to understand the transcriptional basis of this diversity, we collected more than 170 neuronal and non-neuronal cell type-specific transcriptomes defined operationally by transgenic mouse lines and anatomical regions. The dataset indicates that the genes specifically expressed in neuronal cell types are biased toward long genes. We revealed that these long genes have higher capacities to be differentially expressed between cell types and thus assume an important role in diversification of the neuronal transcriptomes. Since mobile element insertions are the main cause of the gene elongations, we propose that exaptation of the inserted mobile elements significantly contributed to the neuronal diversity. Overall design: Examination of whole cell transcriptomes in 174 cell types.
Mapping the transcriptional diversity of genetically and anatomically defined cell populations in the mouse brain.
Sex, Specimen part, Cell line, Subject
View SamplesQuiescent splenic B cells purified from Cg1-cre Prmt5F/F cells and Cg1-cre control mice. Resting B cells were plated on feeder cells expressing CD40L and BAFF and supplemented with IL-4 for activation. Four days later, the resulting activated germinal center-like B cells were purified and RNA extracted and processed for HiSeq. Four independent samples of each genotype were processed and analyzed. Overall design: 2 Experiments, 2 samples of each genotype per experiment (Exp 1: Samples 1,2,7,8 ; Exp 2: Samples 3,4,5,6)_ PRMT5 FF Cg1cre: Samples 1,2,3,4_ Cg1cre controls: Samples 5,6,7,8
PRMT5 is essential for B cell development and germinal center dynamics.
Cell line, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Cis-transcriptional variation in maize inbred lines B73 and Mo17 leads to additive expression patterns in the F1 hybrid.
No sample metadata fields
View SamplesWe found that the midgut shows striking regional differentiation along its anterior-posterior axis. Ten distinct subregions differ in cell morphology, gene expression and aspects of Notch signaling. RNA from isolated regions that was analyzed by RNAseq revealed spatially regulated expression of hundreds of enzymes and other genes with likely tissue functions. Overall design: 10 midgut segments comprising from 1-3 subregions x 3 replicates from each segment = 30 samples
Physiological and stem cell compartmentalization within the Drosophila midgut.
Cell line, Subject
View SamplesMicroarray analysis of gene expression patterns in immature ear, seedling, and embryo tissues from the maize inbred lines B73 and Mo17 identified numerous genes with variable expression. Some genes had detectable expression in only one of the two inbreds; most of these genes were detected in the genomic DNA of both inbreds, indicating that the expression differences are likely caused by differential regulation rather than by differences in gene content. Gene expression was also monitored in the reciprocal F1 hybrids B73xMo17 and Mo17xB73. The reciprocal F1 hybrid lines did not display parental effects on gene expression levels. Approximately 80% of the differentially expressed genes displayed additive expression patterns in the hybrids relative to the inbred parents. The approximately 20% of genes that display nonadditive expression patterns tend to be expressed at levels within the parental range, with minimal evidence for novel expression levels greater than the high parent or less than the low parent. Analysis of allele-specific expression patterns in the hybrid suggested that intraspecific variation in gene expression levels is largely attributable to cis-regulatory variation in maize. Collectively, our data suggest that allelic cis-regulatory variation between B73 and Mo17 dictates maintenance of inbred allelic expression levels in the F1 hybrid, resulting in additive expression patterns.
Cis-transcriptional variation in maize inbred lines B73 and Mo17 leads to additive expression patterns in the F1 hybrid.
No sample metadata fields
View Samples