Nucleosome organization and dynamics play a central role in controlling the DNA accessibility to regulatory factors of many critical cellular functions, especially gene regulation. However, despite extensive studies, the main factors determining nucleosome positioning and its fluctuation during cell cycle still remain elusive. Here, we present a large-scale study of nucleosome plasticity throughout the cell cycle and its interplay with gene expression based on genome-wide nucleosome positioning and mRNA abundance. We have clusterized distinct nucleosome architectures around transcription start sites and replication origins and studied their dynamics during the cell cycle progression. The most significant cell cycle-dependent changes occur at G1-S and G2-M transitions due to a large changes in gene expression in cell cycle regulatory genes. Taken together, our accurate study provides a dynamic picture of chromatin organization along cell cycle and its interplay with gene expression.
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Treatment
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part, Cell line, Treatment
View SamplesType 2 diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting that a crosstalk between mitochondria and the insulin-signaling cascade could be involved in the etiology of TD2 and insulin resistance. In this study, we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the largest genome-wide meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found significant enrichment of T2D-associated SNPs in the genomic context of our linker genes, including four already confirmed and 14 additional SNPs, which when combined were also associated with increased fasting glucose levels according to MAGIC genome-wide meta-analysis (p = 2.8 x 10-7). This study highlights the potential of combining systems biology, experimental, and genome-wide meta-analyses mining for identifying novel genetic variants that increase vulnerability to complex diseases.
No associated publication
Specimen part, Cell line, Treatment
View SamplesType 2 diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting that a crosstalk between mitochondria and the insulin-signaling cascade could be involved in the etiology of TD2 and insulin resistance. In this study, we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the largest genome-wide meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found significant enrichment of T2D-associated SNPs in the genomic context of our linker genes, including four already confirmed and 14 additional SNPs, which when combined were also associated with increased fasting glucose levels according to MAGIC genome-wide meta-analysis (p = 2.8 x 10-7). This study highlights the potential of combining systems biology, experimental, and genome-wide meta-analyses mining for identifying novel genetic variants that increase vulnerability to complex diseases.
No associated publication
Specimen part
View SamplesType 2 diabetes (T2D) is a highly prevalent chronic metabolic disease with strong co-morbidity with obesity and cardiovascular diseases. There is growing evidence supporting that a crosstalk between mitochondria and the insulin-signaling cascade could be involved in the etiology of TD2 and insulin resistance. In this study, we investigated the molecular basis of this crosstalk by using systems biology approaches. We combined, filtered and interrogated different types of functional interaction data, such as direct protein-protein interactions, co-expression analyses and metabolic and signaling dependencies. As a result, we constructed the mitochondria-insulin (MITIN) network, which highlights 286 genes as candidate functional linkers between these two systems. The results of internal gene expression analysis of three independent experimental models of mitochondria and insulin signaling perturbations further support the connecting roles of these genes. In addition, we further assessed whether these genes are involved in the etiology of T2D using the largest genome-wide meta-analysis from the DIAGRAM consortium, involving 8,130 T2D cases and 38,987 controls. We found significant enrichment of T2D-associated SNPs in the genomic context of our linker genes, including four already confirmed and 14 additional SNPs, which when combined were also associated with increased fasting glucose levels according to MAGIC genome-wide meta-analysis (p = 2.8 x 10-7). This study highlights the potential of combining systems biology, experimental, and genome-wide meta-analyses mining for identifying novel genetic variants that increase vulnerability to complex diseases.
No associated publication
Specimen part, Cell line, Treatment
View SamplesDifferential gene expression assessed in siTNF-OMe-P treated animals showed significant correlation between improved colon integrity and clinical parameters of colitis with reduced TLR activation, tissue regeneration and reduced pro-inflammatory cytokines, as compared to all treatment groups.
Functionally enhanced siRNA targeting TNFα attenuates DSS-induced colitis and TLR-mediated immunostimulation in mice.
Specimen part, Treatment
View SamplesMutants in the Drosophila gene lethal (3) malignant brain tumor cause malignant growth in the larval brain. This data shows the changes in gene expression profile associated to mutations in l(3)mbt, both in situ in third instar larval brains and in tumors cultured for 1 5 and 10 (T1, T5, T10) rounds of allograft culture
Ectopic expression of germline genes drives malignant brain tumor growth in Drosophila.
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View SamplesThis SuperSeries is composed of the SubSeries listed below.
The transcription factor GATA6 enables self-renewal of colon adenoma stem cells by repressing BMP gene expression.
Specimen part, Cell line
View SamplesThis SuperSeries is composed of the SubSeries listed below.
dKDM5/LID regulates H3K4me3 dynamics at the transcription-start site (TSS) of actively transcribed developmental genes.
Specimen part
View SamplesExcessive fat accumulation is a major risk factor for the development of type 2 diabetes.To determine the mechanisms by wich TP53INP2 regulates adipogenesis, gene expression profile was performed in TP53INP2-deficient 3T3-L1 cells at different stages of differentiation.
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Specimen part, Cell line, Time
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