Factors and Mechanisms That Influence Chromatin-Mediated Enhancer–Promoter Interactions and Transcriptional Regulation

SIMPLE SUMMARY: The physical interactions between enhancers and promoters create chromatin conformations involved in gene regulation. In cancer cells, the chromatin conformations can be altered with uncontrolled deposition of histone marks resulting in varied gene expression. Although it is not entirely comprehensive how chromatin-mediated enhancer–promoter (E–P) interactions with various histone marks can affect gene expression, this proximity has been observed in multiple systems at multiple loci and is thought to be essential to control gene expression. In this review, we focus on emerging views of chromatin conformations associated with the E–P interactions and factors that establish or maintain such interactions, which may regulate gene expression. ABSTRACT: Eukaryotic gene expression is regulated through chromatin conformation, in which enhancers and promoters physically interact (E–P interactions). How such chromatin-mediated E–P interactions affect gene expression is not yet fully understood, but the roles of histone acetylation and methylation, pioneer transcription factors, and architectural proteins such as CCCTC binding factor (CTCF) and cohesin have recently attracted attention. Moreover, accumulated data suggest that E–P interactions are mechanistically involved in biophysical events, including liquid–liquid phase separation, and in biological events, including cancers. In this review, we discuss various mechanisms that regulate eukaryotic gene expression, focusing on emerging views regarding chromatin conformations that are involved in E–P interactions and factors that establish and maintain them.