Potential roles of super enhancers in inflammatory gene transcription

Abstract

Acute and chronic inflammation is a basic pathological event that contributes to atherosclerosis, cancer, infectious diseases, and immune disorders. Inflammation is an adaptive process to both external and internal stimuli experienced by the human body. Although the mechanism of gene transcription is highly complicated and orchestrated in a timely and spatial manner, recent developments in next-generation sequencing, genomeediting, cryo-electron microscopy, and single cell-based technologies could provide us with insights into the roles of super enhancers (SEs). Initially, SEs were implicated in determining cell fate; subsequent studies have clarified that SEs are associated with various pathological conditions, including cancer and inflammatory diseases. Recent technological advances have unveiled the molecular mechanisms of SEs, which involve epigenetic histone modifications, chromatin three-dimensional structures, and phaseseparated condensates. In this review, we discuss the relationship between Abbreviations 3C, chromosome conformation capture; ATAC-seq, assay for transposase-accessible chromatin using sequencing; BACH2, BTB domain and CNC homolog 2; BET, bromodomain and extra-terminal; BRD2/3/4, bromodomain containing 2/3/4/; BRDT, bromodomain testis associated; BRG1/SMARCA4, SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily a, member 4; C/EBPa, CCAAT enhancer binding protein alpha; CBP, CREB binding protein; CCL, C-C motif chemokine ligand; CDK, cyclin-dependent kinase; ChIA-PET, chromatin interaction analysis by paired-end tag sequencing; ChIP-seq, chromatin immunoprecipitation followed by sequencing; CKIa, casein kinase 1A1; CRISPR, clustered regularly interspaced short palindromic repeats; CTCF, CCCTC-binding factor; CTD, C-terminal domain; CXCL, C-X-C motif chemokine ligand; EBF1, EBF transcription factor 1; EDN1, endothelin 1; ERG, ETS-related gene; eRNA, enhancer RNA; ES, embryonic stem; Esrrb, estrogen related receptor beta; GATA2, GATA binding protein 2; GR, nuclear receptor subfamily 3 group C member 1; GTF, general transcription factor; H3K27ac, acetylation of lysine 27 in histone H3; H3K27me3, trimethylation of lysine 27 in histone H3; H3K4me1, monomethylation of lysine 4 in histone H3; H3K4me2, dimethylation of lysine 4 in histone H3; H3K4me3, trimethylation of lysine 4 in histone H3; H3K9me2, dimethylation of lysine 9 in histone H3;

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“…Recent studies have suggested that bio-macromolecular condensates form at super-enhancers (SEs) [ 81 , 96 , 97 , 100 , 101 ]. This model was supported inter alia by the ability of BRD4 and MED1, a key component of SEs, to form condensates at sites of SE-driven transcription.…”