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, 40 (3), 169-177

Functional Enhancers As Master Regulators of Tissue-Specific Gene Regulation and Cancer Development


Functional Enhancers As Master Regulators of Tissue-Specific Gene Regulation and Cancer Development

Je Yeong Ko et al. Mol Cells.


Tissue-specific transcription is critical for normal development, and abnormalities causing undesirable gene expression may lead to diseases such as cancer. Such highly organized transcription is controlled by enhancers with specific DNA sequences recognized by transcription factors. Enhancers are associated with chromatin modifications that are distinct epigenetic features in a tissue-specific manner. Recently, super-enhancers comprising enhancer clusters co-occupied by lineage-specific factors have been identified in diverse cell types such as adipocytes, hair follicle stem cells, and mammary epithelial cells. In addition, noncoding RNAs, named eRNAs, are synthesized at super-enhancer regions before their target genes are transcribed. Many functional studies revealed that super-enhancers and eRNAs are essential for the regulation of tissue-specific gene expression. In this review, we summarize recent findings concerning enhancer function in tissue-specific gene regulation and cancer development.

Keywords: cell-type specific gene regulation; eRNA; enhancer; epigenetic regulation; super-enhancer.


Fig. 1
Fig. 1. Overview of enhancer features controlling tissue-specific gene expression
Histone modifications to identify active enhancers marked with high H3K27ac, high H3K4me1, and low/no H3K4me3. Super-enhancers are characterized by multiple enhancers co-occupied with lineage-specific transcription factors within tens of kilobases covered with extended H3K27ac. eRNAs are bi-directionally transcribed at enhancers and involved in promoter-enhancer interactions by binding with cohesin.
Fig. 2
Fig. 2. Cancer-specific transcription regulated by super-enhancers and enhancer RNA
(A) Enrichment of super-enhancer associated with the MYC gene family in colorectal cancer and small cell lung cancer cell lines (B) TAL1 super-enhancer in T cell acute lymphoblastic leukemia cell lines (C) Stabilization of E2/ERα/eRNA-induced enhancer-promoter looping in breast cancer cell lines.

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