Abstract
BackgroundSuper-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and differentiation. In addition, the enrichment of disease-associated single nucleotide polymorphism in super-enhancers indicates their critical function in disease-specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation.ResultsIn this study, through a comprehensive analysis of super-enhancers in 30 human cell/tissue types, we identified a new class of super-enhancers which are constitutively active across most cell/tissue types. These ‘common’ super-enhancers are associated with universally highly expressed genes in contrast to the canonical definition of super-enhancers that assert cell-type specific gene regulation. In addition, the genome sequence of these super-enhancers is highly conserved by evolution and among humans, advocating their universal function in genome regulation. Integrative analysis of 3D chromatin loops demonstrates that, in comparison to the cell-type specific super-enhancers, the cell-type common super-enhancers present a striking association with rapidly recovering loops.ConclusionsIn this study, we propose that a new class of super-enhancers may play an important role in the early establishment of 3D chromatin structure.
Highlights
Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and differentiation
Our analysis suggests that a substantial number of super-enhancers exhibits prevalent activities across cell-types in terms of Histone H3 lysine acetylation (H3K27ac) signals and that these non-canonical super-enhancers are involved in the formation of fast recovering chromatin loops
Genomic landscape of super-enhancer domains To characterize different modes of super-enhancers across various human cell/tissue types, we first investigated the genomic distribution of super-enhancers across 30 human cell/ tissue types, including 5 H1-derived early lineages, 8 immortalized cell lines, and 17 human postmortem tissues
Summary
Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation during development and differentiation. The enrichment of disease-associated single nucleotide polymorphism in super-enhancers indicates their critical function in disease-specific gene regulation. Little is known about the function of super-enhancers beyond gene regulation. Super-enhancers or stretch enhancers are defined by a strong enrichment of mediators and transcription-regulating proteins, appearing to play a deterministic role in cellular identity by controlling the expression of cell-type specific genes [1, 2]. Previous studies have revealed the critical function of super-enhancers during development and differentiation [3]. The enrichment of disease-associated single nucleotide polymorphism (SNP) in super-enhancers compared to that of typical enhancers proposed a substantial link between super-enhancers and many complex human diseases [2].
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