“…To investigate these “minor changes”, a number of 3D genomics techniques have been developed. These include chromosome conformation capture (3C)-based technologies, such as chromosome conformation capture-on-chip (4C) [ 34 ], chromosome conformation capture carbon copy (5C) [ 35 ], high-throughput/resolution chromosome conformation capture (Hi-C) [ 36 ], Single-cell Hi-C [ 37 ], eHi-C [ 38 ], in 3D genomics, chromatin interaction analysis by paired-end tag sequencing (ChIA-PET) [ 39 ], and related methods, which have enabled the discovery of transcriptional regulatory elements, especially enhancers, and their effects on gene expression ( Figure 1 ). In addition, various methods, such as self-transcribing active regulatory region sequencing (STARR-seq), chromatin immunoprecipitation sequencing (ChIP-seq) [ 40 , 41 ], DNase-seq, site-specific integration FACS-sequencing (SIF-seq), assay for transposase accessible chromatin with high-throughput sequencing (ATAC-seq), robust statistical estimation (ROSE) algorithm, in situ Hi-C followed by chromatin immunoprecipitation (HiChIP), have been widely used for the identification and annotation of enhancers and super enhancers (annotations of enhancer and super enhancer are described in detail in Section 4 ).…”