A new class of constitutively active super-enhancers is associated with fast recovery of 3D chromatin loops

Autor: Hyunwoong Kim, Inkyung Jung, Jayoung Ryu, Dongchan Yang, Andrew J. Lee
Rok vydání: 2019
Předmět:
animal structures
Cell
information science
Genomics
Computational biology
Biology
lcsh:Computer applications to medicine. Medical informatics
Biochemistry
Cell Line
03 medical and health sciences
0302 clinical medicine
Super-enhancer
Structural Biology
parasitic diseases
medicine
Humans
natural sciences
Enhancer
Molecular Biology
Gene
lcsh:QH301-705.5
030304 developmental biology
Chromatin loops
Whole genome sequencing
Regulation of gene expression
0303 health sciences
Applied Mathematics
Research
technology
industry
and agriculture
virus diseases
Chromatin
Computer Science Applications
Gene regulation
medicine.anatomical_structure
Enhancer Elements
Genetic
Gene Ontology
lcsh:Biology (General)
3D chromatin structure
030220 oncology & carcinogenesis
lcsh:R858-859.7
Nucleic Acid Conformation
DNA microarray
Function (biology)
Zdroj: BMC Bioinformatics
BMC Bioinformatics, Vol 20, Iss S3, Pp 25-36 (2019)
ISSN: 1471-2105
Popis: Super-enhancers or stretch enhancers are clusters of active enhancers that often coordinate cell-type specific gene regulation. However, little is known about the function of super-enhancers beyond gene regulation. In 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. We propose that a new class of super-enhancers may play an important role in the early establishment of 3D chromatin structure.BackgroundSuper-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]. In addition, a set of recent studies have proposed potential functions of super-enhancers in the extremely long-range chromatin communications and the establishment of 3D chromatin loops[4]. These results suggest a more universal role of super-enhancers in genome regulation apart from cell-type specific gene regulation, but little is known about the mechanisms underlying these various functions. To extend the current knowledge of super-enhancers and their biological roles, we conducted a comprehensive analysis of super-enhancer activities across 30 human cell/tissue types. Our analysis suggests that a substantial number of super-enhancers exhibits prevalent activities across cell-types in terms of H3K27ac signals, and that these non-canonical super-enhancers are involved in the formation of fast recovering chromatin loops.NoteA genome browser session has been set up for visualization of the super-enhancer domains described in the current study– https://genome.ucsc.edu/cgi-bin/hgTracks?hgS-doOtherUser=submit&hgS-otherUserName=abundantiavosliberabit&hgS-otherUserSessionName=SuperEnhancerDomain
Databáze: OpenAIRE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje