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SMAD3 targets in A549 lung epithelial cells

ABSTRACT: TGFβ activates a signal transduction cascade that results in the transcription of genes, primarily through the DNA-binding transcription factor SMAD3. The objective of this study is to identify SMAD3 binding targets and the molecular pathways affected by the TGFβ1/SMAD3 signal transduction on a genome-wide scale.

ORGANISM(S): Homo sapiens

PROVIDER: GSE26858 | GEO | 2011/06/24

SECONDARY ACCESSION(S): PRJNA135983

REPOSITORIES: GEO

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SMAD3 targets in A549 lung epithelial cells

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SMAD3 ChIP-on-chip on A549 cell line

Project description:The aim of this study is to identify SMAD3 binding targets affected by the TGFb1/SMAD3 signal transduction on a genome-wide scale Formaldehyde cross-linked, sonicated chromatin was prepared from non-stimulated A549 cell line and stimulated with TGFb1. Chromatin immunoprecipated with anti-SMAD3 antibody is labeled with Cy5 and mock IP (with anti-FLAG antibody) is labeled with Cy3 and co-hybridized on Agilent Human Promoter Set arrays. Two biological replicates were performed.

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Genomic binding profiles for ZNF165, ZNF446, and SMAD3 in triple-negative breast cancer

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TGFB signaling effect on cultured NHLF cells

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Data from the paper Context-specific Effects of TGFβ/SMAD3 in Cancer Are Modulated by the Epigenome. Tufegdzic et al, Cell Reports 2015

Project description:The transforming growth factor beta (TGFβ) signalling pathway exerts opposing effects on cancer cells, acting either as a tumor-promoter or as a tumor-suppressor. Here we show these opposing effects are a result of the synergy between SMAD3, a downstream effector of TGFβ signalling, and the distinct epigenomes of breast tumor initiating cells (BTICs). These effects of TGFβ are associated with distinct gene expression programs, but genomic SMAD3 binding patterns are highly similar in the BTIC-promoting and BTIC- suppressing contexts. Our data show cell type-specific epigenetic configurations provide a modulatory layer by determining accessibility of genes to regulation by TGFβ/SMAD3. LBH, one such context-specific target gene, is regulated according to its DNA methylation status, and is crucial for TGFβ-dependent promotion of BTICs. Overall, these results reveal that the epigenome plays a central and previously overlooked role in shaping the context-specific effects of TGFβ in cancer.

| EGAS00001001570 | EGA

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