Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synergistic model of chromatin predicts Dnase-I accessibility

ABSTRACT: Enhancers and promoters commonly occur in accessible chromatin characterized by depleted nucleosome contact; however, it is unclear how chromatin accessibility is governed. We show that a logic of cis-acting DNA sequence features can predict the majority of chromatin accessibility at high spatial resolution. We develop a new type of high-dimensional machine learning model, the Cooperative Chromatin Model (CCM), that is capable of predicting a large fraction of genome-widepromoters chromatin accessibility at basepair-resolution in a range of human and mouse cell types from DNA sequence alone. We confirm that a CCM accurately predicts chromatin accessibility, even of a vast array of synthetic DNA sequences, with a novel CrispR-based method of highly efficient site-specific DNA library integration. CCMs are directly interpretable and reveal that a logic based on local, non-specific cooperation, largely among pioneer TFs, is sufficient to predict a large fraction of cellular chromatin accessibility in a wide variety of cell types.

ORGANISM(S): Mus musculus Homo sapiens

PROVIDER: GSE80105 | GEO | 2016/07/20

SECONDARY ACCESSION(S): PRJNA318029

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Chromatin Accessibility in Developing Human Brain

Project description:<p>Non-coding regions comprise most of the human genome and harbor a significant fraction of risk alleles for neuropsychiatric diseases, yet their functions remain poorly defined. We created a high-resolution map of non-coding elements involved in human cortical neurogenesis by contrasting chromatin accessibility and gene expression in the germinal zone and cortical plate of the developing cerebral cortex. To obtain a high resolution depiction of chromatin structure and gene expression in developing human fetal cortex, we dissected the post-conception week (PCW) 15-17 human neocortex into two major anatomical divisions to distinguish between proliferating neural progenitors and post mitotic neurons: (1) GZ: the neural progenitor-enriched region encompassing the ventricular zone (VZ), subventricular zone (SVZ), and intermediate zone (IZ) and (2) CP: the neuron-enriched region containing the subplate (SP), cortical plate (CP), and marginal zone (MZ). Tissues were obtained from three independent donors and three to four technical replicates from each tissue were processed for ATAC-seq to define the landscape of accessible chromatin and RNA-seq for genome-wide gene expression profiling.</p>

| phs001438 | dbGaP

Role of pericytes in the development of cerebral cavernous malformations

Project description:Cerebral cavernous malformation (CCM) is caused by loss-of-function mutations in CCM1, CCM2, or CCM3 genes of endothelial cells. It is characterized by pericyte deficiency. However, the role of pericytes in CCMs remains poorly understood. Our study showed that pericytes in Cdh5CreERT2; Ccm1fl/fl (Ccm1ECKO) mice were high expression of PDGFRβ. The inhibition of pericyte function by CP-673451 aggravated the CCM lesion development. RNA-seq analysis revealed the molecular traits of pericytes, such as highly expressed ECM-related genes, especially Fn1. Furthermore, KLF4 coupled with phosphorylated SMAD3 promoted the transcription of fibronectin in pericytes of CCM lesions. RGDS peptide, an inhibitor of fibronectin, decreased the lesion area in the cerebella and retinas of Ccm1ECKO mice. Also, human CCM lesions had abundant fibronectin deposition, and pSMAD3- and KLF4-positive pericytes. The current data demonstrated that pericytes are essential for CCM lesion development, and fibronectin intervention may provide a novel target for therapeutic intervention in such patients.

2022-12-07 | GSE213244 | GEO

Epigenetic regulation by Polycomb Repressive Complex 1 promotes Cerebral Cavernous Malformations

Project description:Cerebral cavernous malformations (CCMs) are anomalies that develop mainly in the cerebral vasculature. They result from mutations in CCM1/KRIT1, CCM2, or CCM3/PDCD10. Loss of CCM proteins triggers a MAPK-Krüppel-like factor 2 (KLF2) signaling cascade, which induces a pathophysiological pattern of gene expression within endothelial cells. The downstream target genes that are activated by KLF2 are mostly unknown. Here we show that Chromobox Protein Homolog 7 (CBX7), component of the Polycomb Repressive Complex 1, contributes to pathophysiological KLF2 signaling during zebrafish cardiovascular development. CBX7/cbx7a mRNA is strongly upregulated in lesions of CCM patients, and in human, mouse, and zebrafish CCM-deficient endothelial cells. The silencing or pharmacological inhibition of CBX7/Cbx7a suppresses pathological CCM phenotypes in ccm2 zebrafish, CCM2-deficient HUVECs, and in a pre-clinical murine CCM3 disease model. Whole-transcriptome datasets from zebrafish cardiovascular tissues and human endothelial cells reveal that CBX7/Cbx7a plays a role in the activation of KLF2 targets including genes encoding TEK, Angiopoietin1, WNT9, and endoMT proteins. Our findings uncover an intricate interplay in the regulation of Klf2-dependent biomechanical signaling by CBX7 in CCM. This work also provides insights for therapeutic strategies in the pathogenesis of CCM.

2024-09-20 | GSE277234 | GEO

Global decay of regulatory chromatin architecture promotes rebalancing of gene expression during colorectal cancer development [Hi-C]

Project description:Although the 3D genome architecture is essential for long-range gene regulation, the significance of physical chromatin interactions is challenged by recent findings of mutual insensitiveness between contact propensity and gene expression. Here we report hundred basepair-resolution profiling of chromatin conformation in 33 colon tissues tracing the formation and malignant transformation of colorectal polyps. We identified progressive genome-wide decays of chromatin structures such as interaction stripes and loops on all types of cis-regulatory elements, particularly promoters, independent to the alterations of DNA methylation and chromatin accessibility. Instead of linearly correlated with degree of structural decays, transcription levels shifted toward correction of their quantitative mismatching with corresponding promoter contact propensity. These observations suggest increasing sensitivity of transcription to regulatory architecture integrity along with its loss during early cancer development, a mechanism which may provide novel insights to the misregulations of cancer driving genes.

2022-08-29 | GSE207951 | GEO

Global decay of regulatory chromatin architecture promotes rebalancing of gene expression during colorectal cancer development [ATAC-Seq]

2022-08-29 | GSE207950 | GEO

Global decay of regulatory chromatin architecture promotes rebalancing of gene expression during colorectal cancer development [RNA-Seq]

2022-08-29 | GSE207949 | GEO

Global decay of regulatory chromatin architecture promotes rebalancing of gene expression during colorectal cancer development [RNA-seq II]

2024-02-11 | GSE255300 | GEO

Developmental Venous Anomalies are a Genetic Primer for Cerebral Cavernous Malformations

Project description:Purpose: Cerebral cavernous malformations (CCMs) are hemorrhagic neurovascular malformations that may lead to stroke, seizures and other clinical sequelae. Recent studies have shown that somatic mutations in MAP3K3 and PIK3CA also contribute to CCM pathogenesis; however, it remains unclear how these mutations contribute to sporadic versus familial cases. In our previous research, we’ve shown that co-occurring MAP3K3 and PIK3CA mutations are present within the same clonal population of cells. The overall goal of this study was to identify PIK3CA mutations in CCM-associated developmental venous anomalies (DVA). We also analyzed the plasma miRNome of patients with (1) DVA without associated CCM, as well as (2) DVA with an associated CCM) to identify circulating miRNAs that might serve as biomarkers reflecting PIK3CA activity. Methods: We collected and sequenced the plasma miRNome of 12 individuals with a sporadic CCM associated with a DVA (CCM + DVA), 6 individuals with a DVA without a CCM (DVA only), and 7 healthy controls. Results: We found that the identical PIK3CA mutation is found in endothelial cells of both the DVA and its associated CCM, but that an activating MAP3K3 mutation appears only in the CCM. The analyses miR-134-5p was downregulated in the groups of patients with only a DVA only group (when compared to healthy controls). This miRNA has been shown to target PIK3CA. In addition, miR-182-5p, was upregulated and targets MAP3K3; while let-7c-5p was downregulated and targets both PIK3CA and MAP3K3 in the group of patients with CCM and an associated DVA (when compared to DVA only). Conclusions: These results support a mechanism where DVA develop as the result of a PIK3CA mutation, creating a region of the brain vasculature that functions as a genetic primer for CCM development following acquisition of an additional somatic mutation.

2022-02-06 | GSE195732 | GEO

Temporal Analyses of Cardiac Chromatin Accessibility, DNA Methylation and Epigenomic Structure Reveal Locus-Specific Regulation [RRBS]

Project description:Heart failure can be induced or ameliorated by regulation of chromatin modifying enzymes. Because so many chromatin factors regulate gene expression, we used ATAC-seq to report the status of a given locus at any time—the sum total of all epigenetic modifiers—in a mouse model of pressure overload hypertrophy. Early compensation of pressure overload at 3 days was associated with widespread changes in chromatin accessibility and DNA methylation, the majority of which persisted to the decompensated phase (3 weeks), revealing the temporal nature of epigenomic compensation to pathologic stimuli. A cardiac-specific CTCF depletion model was used to examine how this protein maintains basal cardiac chromatin function and revealed that loss of CTCF causes widespread changes in accessibility and methylation that are distinct from those in pressure overload. Less than half of the gene expression changes occurring at either time point after pressure overload were explained by the actions of DNA methylation alone and accessibility was likewise an imperfect predictor of transcription. Distal enhancers were paired with genes based on chromatin structural data and the regulatory actions of these elements examined in the context of DNA methylation and accessibility: enhancer actions require specific combinations of transcription factors and histone modifications at different stages of disease and to execute a specific transcriptional event (methylation and accessibility alone were insufficient to predict the behavior). In summary, these studies characterize the logic employed at different coding, regulatory, and noncoding regions to regulate chromatin accessibility and transcription, providing a resource of epigenomic data at distinct temporal stages of heart failure.

2021-12-01 | GSE154520 | GEO

Temporal Analyses of Cardiac Chromatin Accessibility, DNA Methylation and Epigenomic Structure Reveal Locus-Specific Regulation [RNA-seq]

2021-12-01 | GSE154519 | GEO