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Alternative super-enhancers result in similar gene expression in different tissues

View ORCID ProfileDóra Bojcsuk, View ORCID ProfileGergely Nagy, Bálint László Bálint
doi: https://doi.org/10.1101/329987
Dóra Bojcsuk
1Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Gergely Nagy
2Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Bálint László Bálint
1Genomic Medicine and Bioinformatic Core Facility, Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, Debrecen, Hungary
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Abstract

Super-enhancers (SEs) are clusters of highly active enhancers, regulating cell type-specific and disease-related genes, including oncogenes1–3. The individual regulatory regions within SEs might be simultaneously bound by different transcription factors (TFs) and co-regulators such as P300, BRD4 and Mediator, which together establish a chromatin environment conducting to effective gene induction4–6. While cells with distinct TF profiles can have different functions, an unanswered question is how different cells control overlapping genetic programmes. Here, we show that the construction of oestrogen receptor alpha (ERα)-driven SEs is tissue specific, and both the collaborating TFs and the active SE components are largely differing between human breast cancer-derived MCF-7 and endometrial cancer-derived Ishikawa cells; nonetheless, SEs common to both cell types have similar transcriptional outputs. In the MCF-7 cell line, ERα-dominated SEs are also driven by the well-known FoxA1 and AP2γ TFs, as described previously7, whereas in Ishikawa cells, FoxM1, TCF12 and TEAD4 are as important as ERα for SE formation. Our results show that SEs can be constructed in several ways, but the overall activity of common SEs is the same between cells with a common master regulator. These findings may reshape our current understanding of how these regulatory units can fine-tune cell functions. From a broader perspective, we show that systems assembled from different components can perform similar tasks if a common functional trigger drives their assembly.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 25, 2018.
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Alternative super-enhancers result in similar gene expression in different tissues
Dóra Bojcsuk, Gergely Nagy, Bálint László Bálint
bioRxiv 329987; doi: https://doi.org/10.1101/329987
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Alternative super-enhancers result in similar gene expression in different tissues
Dóra Bojcsuk, Gergely Nagy, Bálint László Bálint
bioRxiv 329987; doi: https://doi.org/10.1101/329987

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