Topology regulatory elements: From shaping genome architecture to gene regulation

Curr Opin Struct Biol. 2023 Nov 4;83:102723. doi: 10.1016/j.sbi.2023.102723. Online ahead of print.ABSTRACTThe importance of 3D genome topology in the control of gene expression is becoming increasingly apparent, while regulatory mechanisms remain incompletely understood. Several recent studies have identified architectural elements that influence developmental gene expression by shaping locus topology. We refer to these elements as topological regulatory elements (TopoREs) to reflect their dual roles in genome organisation and gene expression. Importantly, these elements do not harbour autonomous transcriptional activation capacity, and instead appear to facilitate enhancer-promoter interactions, contributing to robust and precise timing of transcription. We discuss examples of TopoREs from two classes that are either dependent or independent of CTCF binding. Importantly, identification and interpretation of TopoRE function may shed light on multiple aspects of gene regulation, including the relationship between enhancer-promoter proximity and transcription, and enhancer-promoter specificity. Ultimately, understanding TopoRE diversity and function will aid in the interpretation of how human sequence variation can impact transcription and contribute to disease phenotypes.PMID:37931379 | DOI:10.1016/j.sbi.2023.102723

Source: Current Opinion in Structural Biology - November 6, 2023 Category: Biology Authors: Liang-Fu Chen Hannah Katherine Long Source Type: research