- Title
- Super-enhancers in transcriptional regulation and genome organization
- Creator
- Wang, Xi; Cairns, Murray J.; Yan, Jian
- Relation
- NHMRC.1121474 http://purl.org/au-research/grants/nhmrc/1121474
- Relation
- Nucleic Acids Research Vol. 47, Issue 22, p. 11481-11496
- Publisher Link
- http://dx.doi.org/10.1093/nar/gkz1038
- Publisher
- Oxford University Press
- Resource Type
- journal article
- Date
- 2019
- Description
- Gene expression is precisely controlled in a stage and cell-type-specific manner, largely through the interaction between cis-regulatory elements and their associated trans-acting factors. Where these components aggregate in promoters and enhancers, they are able to cooperate to modulate chromatin structure and support the engagement in long-range 3D superstructures that shape the dynamics of a cell's genomic architecture. Recently, the term 'super-enhancer' has been introduced to describe a hyper-active regulatory domain comprising a complex array of sequence elements that work together to control the key gene networks involved in cell identity. Here, we survey the unique characteristics of super-enhancers compared to other enhancer types and summarize the recent advances in our understanding of their biological role in gene regulation. In particular, we discuss their capacity to attract the formation of phase-separated condensates, and capacity to generate three-dimensional genome structures that precisely activate their target genes. We also propose a multi-stage transition model to explain the evolutionary pressure driving the development of super-enhancers in complex organisms, and highlight the potential for involvement in tumorigenesis. Finally, we discuss more broadly the role of super-enhancers in human health disorders and related potential in therapeutic interventions.
- Subject
- super enhancers; cell-type-specific; genome organization; human health disorders
- Identifier
- http://hdl.handle.net/1959.13/1455390
- Identifier
- uon:45083
- Identifier
- ISSN:1362-4962
- Rights
- © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
- Language
- eng
- Full Text
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