Chromatin insulators in gene regulation and 3D genome organization
Hina Sultana, Rohit Kunar, A. Gregory Matera
Abstract
The human genome attains an amazing spatial organization in the packaging of 2 m of DNA into a 10-μm nucleus. Such structural organization is achieved by the folding of chromatin and the regulation exerted by architectural proteins such as insulators. Chromatin insulators are boundary elements of the genome that, through enhancing blocking activities, demarcation of chromatin domains, and chromatin looping, regulate transcription. The review focuses on the identification and characterization of insulators in various species, discussing mainly the functions of the CCCTC-binding factor (CTCF) in mammals and functionally equivalent insulator proteins in Drosophila melanogaster. We review here the mechanisms of enhancer blocking, barrier activity, and loop extrusion, emphasizing their effects on topologically associating domains and chromatin architecture. Furthermore, we discuss new concepts that have come into prominence: tethering elements and redundancy among the insulator proteins, which contribute to chromatin organization. Advances in methodology, including chromosome conformation capture and high-resolution imaging techniques, have transformed our view of the dynamic interplay between the architecture of chromatin and transcription regulation. This review discusses the importance of insulators for genome organization and describes future directions in investigating their roles in both gene regulation and three-dimensional genomic architecture.