The structural and functional roles of CTCF in the regulation of cell type-specific and human disease-associated super-enhancers

Super-enhancers play critical roles in cell-type specific gene controls and human disease progression. CCCTC-binding factor (CTCF), a transcriptional repressor that insulates the expression of neighboring genes and is involved in chromatin interactions, is frequently present in the boundary regions of or within super-enhancers. However, the structural and functional roles of CTCF in regulating super-enhancers remain elusive.To provide a comprehensive review describing the distinct chromatin features and functional roles of CTCF within super-enhancers.This review compares the various tools used to study the three-dimensional (3D) chromatin architecture of super-enhancers; summarizes the chromatin features of CTCF within cell-type specific super-enhancers and their in vivo biological activities, as determined by CRISPR/Cas9 genome editing; and describes the structural and functional activities of CTCF within human disease-associated super-enhancers.This review provides fundamental insights into the regulatory mechanisms of super-enhancers and facilitates studies of tissue-specific developmental processes and human disease progression.