2025/04/12 by Isabelle Seufert, Claire Vargas, Sina Jasmin Wille +1 · 1 voice · 1 citation
Biochemistry, Genetics and Molecular Biology · #Genomics and Chromatin Dynamics #RNA Research and Splicing #Cancer-related gene regulation
paper · pdf · doi:10.1002/ijc.35424
Enhancers are critical regulators of gene expression. Structural variations in cancer genomes can lead to enhancer hijacking, where oncogenes are activated by mistargeted enhancer activity. Novel enhancer-promoter interactions may also arise through chromosomal rearrangements that create extrachromosomal DNA elements. Additionally, fusion proteins and other mutation-induced alterations in protein properties can lead to the aberrant assembly of proteins into large complexes on the size scale of 0.1-1 μm termed onco-condensates. Transcription factors and co-activators accumulate with cis-regulatory elements in these structures, driving oncogenic programs. Here, we review current evidence of how altered genome architecture and macromolecular assembly result in deregulated enhancer-promoter communication. We discuss emerging strategies to exploit these mechanisms for clinical applications.