Transcriptional machinery as an architect of genome structure.

Chromatin organization, facilitated by compartmentalization and loop extrusion, is crucial for proper gene expression and cell viability. Transcription has long been considered important for shaping genome architecture due to its pervasive activity across the genome and impact on the local chromatin environment. Although earlier studies suggested a minimal contribution of transcription to shaping global genome structure, recent insights from high-resolution chromatin contact mapping, polymer simulations, and acute perturbations have revealed its critical role in dynamic chromatin organization at the level of active genes and enhancer-promoter interactions. In this review, we discuss these latest advances, highlighting the direct interplay between transcriptional machinery and loop extrusion. Finally, we explore how transcription of genes and non-coding regulatory elements may contribute to the specificity of gene regulation, focusing on enhancers as sites of targeted cohesin loading.