Abstract
Super-enhancers (SEs) are clusters of highly active enhancers, regulating cell type-specific and disease-related genes, including oncogenes. The individual regulatory regions within SEs might be simultaneously bound by different transcription factors (TFs) and co-regulators, which together establish a chromatin environment conducting to effective transcription. While cells with distinct TF profiles can have different functions, how different cells control overlapping genetic programs remains a question. In this paper, we show that the construction of estrogen receptor alpha-driven SEs is tissue-specific, both collaborating TFs and the active SE components greatly differ between human breast cancer-derived MCF-7 and endometrial cancer-derived Ishikawa cells; nonetheless, SEs common to both cell lines have similar transcriptional outputs. These results delineate that despite the existence of a combinatorial code allowing alternative SE construction, a single master regulator might be able to determine the overall activity of SEs.
Keywords:
ChIP-seq; Ishikawa cell line; MCF-7 cell line; enhancer; estrogen receptor alpha (ERα), transcription factor; super-enhancer.
MeSH terms
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Basic Helix-Loop-Helix Transcription Factors / genetics
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Basic Helix-Loop-Helix Transcription Factors / metabolism
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Binding Sites / genetics
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Breast Neoplasms / genetics
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Breast Neoplasms / metabolism*
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Cell Line, Tumor
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Chromatin Immunoprecipitation Sequencing
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DNA-Binding Proteins / genetics
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DNA-Binding Proteins / metabolism
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E-Box Elements / genetics
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Endometrial Neoplasms / genetics
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Endometrial Neoplasms / metabolism*
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Endometrium / cytology
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Endometrium / metabolism*
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Enhancer Elements, Genetic*
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Estrogen Receptor alpha / genetics
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Estrogen Receptor alpha / metabolism*
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Female
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Forkhead Box Protein M1 / genetics
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Forkhead Box Protein M1 / metabolism
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Gene Expression Regulation, Neoplastic / genetics
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Humans
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MCF-7 Cells
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Muscle Proteins / genetics
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Muscle Proteins / metabolism
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TEA Domain Transcription Factors
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Transcription Factors / genetics
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Transcription Factors / metabolism*
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Transcriptome
Substances
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Basic Helix-Loop-Helix Transcription Factors
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DNA-Binding Proteins
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ESR1 protein, human
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Estrogen Receptor alpha
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FOXM1 protein, human
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Forkhead Box Protein M1
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Muscle Proteins
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TEA Domain Transcription Factors
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TEAD4 protein, human
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Transcription Factors
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TCF12 protein, human