At the Crossroad of Gene Regulation and Genome Organization: Potential Roles for ATP-Dependent Chromatin Remodelers in the Regulation of CTCF-Mediated 3D Architecture

SIMPLE SUMMARY: The way DNA is packaged in the nucleus of a cell is important for when and how genes are expressed. There are many levels of packaging, and new techniques have revealed that long-range interactions are important for both promoting and restricting the transcription of genes. Some long-range interactions are mediated by physical loops in the genome where, like a rubber band, the ring-shaped cohesin complex loops sections of DNA bound by CCCTC-binding factor (CTCF). Both cohesin and CTCF act on DNA, and increasing evidence indicates that their function is inhibited by nucleosomes bound to the DNA. In this review, we summarize the current knowledge of how individual chromatin remodelers, which utilize ATP to move nucleosomes on DNA, facilitate or inhibit cohesin/CTCF-dependent looping interactions. ABSTRACT: In higher order organisms, the genome is assembled into a protein-dense structure called chromatin. Chromatin is spatially organized in the nucleus through hierarchical folding, which is tightly regulated both in cycling cells and quiescent cells. Assembly and folding are not one-time events in a cell’s lifetime; rather, they are subject to dynamic shifts to allow changes in transcription, DNA replication, or DNA damage repair. Chromatin is regulated at many levels, and recent tools have permitted the elucidation of specific factors involved in the maintenance and regulation of the three-dimensional (3D) genome organization. In this review/perspective, we aim to cover the potential, but relatively unelucidated, crosstalk between 3D genome architecture and the ATP-dependent chromatin remodelers with a specific focus on how the architectural proteins CTCF and cohesin are regulated by chromatin remodeling.