Unknown,Transcriptomics,Genomics,Proteomics

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Histone modification analysis in TGFbeta/TNFalpha treated A549 spheroid cultures


ABSTRACT: We studied the extent of chromatin remodeling in an in-vitro model of the epithelial-mesenchymal transition (EMT). EMT is induced in spheroid cultures (3D) using simultaneously two cytokines: TGFbeta and TNFalpha. The epithelial-mesenchymal transition (EMT) is a cellular de-differentiation process that has been implicated in cancer progression and metastasis. Increasing evidence suggests that EMT is regulated and established by epigenetic reprogramming, however a systems-level mechanism describing how chromatin remodeling contributes to the phenotypic switch is not known. We have generated genome-wide maps of 18 histone modifications/variants and variants in both the epithelial and mesenchymal states and quantified patterns of epigenetic changes at gene and enhancer loci. Clusters of these patterns reveal that EMT-related genes and their proximal enhancers are regulated through coordinated patterns of chromatin activation and repression at both gene and enhancer loci. At the cellular level, the remodeling of gene loci translates into a modular protein interaction network that recapitulates EMT-related signaling. Moreover, differentially activated or repressed enhancers are associated with two non-overlapping sets of transcription factors. We propose a chromatin-mediated regulatory feedback loop model where the NFkappaB and AP-1 transcription factors (TFs) bind activated enhancers, that regulate EMT-related genes, which in turn activate signaling pathways upstream of these TFs.

ORGANISM(S): Homo sapiens

SUBMITTER: Marcin Cieslik 

PROVIDER: E-GEOD-42374 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Epigenetic coordination of signaling pathways during the epithelial-mesenchymal transition.

Cieślik Marcin M   Hoang Stephen A SA   Baranova Natalya N   Chodaparambil Sanjay S   Kumar Manish M   Allison David F DF   Xu Xiaojiang X   Wamsley J Jacob JJ   Gray Lisa L   Jones David R DR   Mayo Marty W MW   Bekiranov Stefan S  

Epigenetics & chromatin 20130902 1


<h4>Background</h4>The epithelial-mesenchymal transition (EMT) is a de-differentiation process required for wound healing and development. In tumors of epithelial origin aberrant induction of EMT contributes to cancer progression and metastasis. Studies have begun to implicate epigenetic reprogramming in EMT; however, the relationship between reprogramming and the coordination of cellular processes is largely unexplored. We have previously developed a system to study EMT in a canonical non-small  ...[more]

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