Regulation and Function of Repetitive Sequences in the Genome: From Epigenetic Silencing to Evolutionary Innovation and Disease

Repetitive DNA sequences, including transposable elements, satellite DNA, and simple sequence repeats, form the structural and functional backbone of most eukaryotic genomes. Long regarded as “junk” or non-functional DNA, these repetitive elements are now recognized as integral genomic components engaged in diverse regulatory and structural functions. Advances in high-resolution sequencing, epigenomic profiling, and three-dimensional genome mapping have revealed that these sequences participate in essential cellular processes through tightly controlled epigenetic networks. DNA methylation, histone modifications such as H3K9me3 and H3K27me3, and small RNA-mediated silencing pathways collectively restrain transposable element activity, thus maintaining genomic stability. Dysregulation of these controls has been implicated in cancer, neurodegenerative, and autoimmune diseases, while new studies continue to uncover their contributions to chromatin organization and nuclear architecture. Despite such progress, comprehensive understanding of how repetitive sequences transition from potential genomic instigators to functional regulators and evolutionary drivers remains incomplete. Further integrative research is needed to dissect the mechanistic interplay between epigenetic silencing, chromatin regulation, and disease manifestation.This Research Topic aims to advance mechanistic and functional understanding of repetitive DNA sequences, moving beyond descriptive observations to uncover their active roles in genome regulation, organismal development, and pathology. It seeks to elucidate how epigenetic networks modulate repetitive sequence function, how these sequences contribute to the maintenance and plasticity of chromatin architecture, and how their dysregulation underpins disease processes. Key questions include how silencing mechanisms are dynamically regulated across cell types and life stages, how repeats participate in gene expression control and chromosomal organization, and how they serve as sources of evolutionary and biological innovation. Ultimately, this Research Topic aims to integrate basic research with translational perspectives, identifying new biomarkers and potential therapeutic avenues associated with repetitive genome elements.To gather further insights into the molecular, evolutionary, and biomedical significance of repetitive DNA sequences, this Research Topic welcomes studies encompassing a broad but defined range of investigations. We encourage multidisciplinary contributions integrating genomics, epigenetics, structural biology, evolutionary biology, and clinical research. The following themes are particularly relevant:o Mechanisms of epigenetic silencing of transposable elements and other repetitive sequences, involving DNA methylation, histone modifications, and small RNA pathways.o Functional roles of repetitive sequences in three-dimensional chromatin organization, nuclear compartmentalization, and heterochromatin formation.o Regulatory impacts of repeat elements on nearby gene expression, including enhancer, promoter, or insulator activities.o Evolutionary functions of repeats in generating genetic novelty and developmental innovations, including element domestication and adaptive evolution.o Pathogenic consequences of repetitive sequence dysregulation in cancer, neurodegenerative, and autoimmune diseases.o Translational applications such as repeat-based biomarkers, epigenetic signatures, and gene therapy strategies targeting repeat function or silencing.o Technological innovations enabling high-resolution exploration of repetitive sequences, including long-read sequencing, single-cell and spatial epigenomics, and CRISPR-based functional profiling. Topic editors: Yuanyan Xiong, Zhenhua Luo, Guang Shi, Kaimeng Huang Source: https://www.frontiersin.org/research-topics/82406/regulation-and-function-of-repetitive-sequences-in-the-genome-from-epigenetic-silencing-to-evolutionary-innovation-and-disease