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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

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.

Click on a Dataset ID in the table below to learn more, and to find out who to contact about access to these data

Dataset ID Description Technology Samples
EGAD00001001667 Illumina MiSeq 12
EGAD00001001668 Illumina HiSeq 2500 12
EGAD00001001669 Illumina HiSeq 2500 42
EGAD00010000859 Illumina ChIP-Sequencing 16
EGAD00010000860 Illumina ChIP-Sequencing 16
EGAD00010000862 Illumina ChIP-Sequencing 16
EGAD00010000863 Illumina ChIP-Sequencing 16
EGAD00010000865 Illumina MBD-Sequencing 16
EGAD00010000867 Illumina beadarray 16
EGAD00010000868 Illumina Bisulfite-Sequencing 16
Publications Citations
Context-Specific Effects of TGF-β/SMAD3 in Cancer Are Modulated by the Epigenome.
Cell Rep 13: 2015 2480-2490
The testis protein ZNF165 is a SMAD3 cofactor that coordinates oncogenic TGFβ signaling in triple-negative breast cancer.
Elife 9: 2020 e57679