While the genome serves as the instruction manual encoding all biological functions in our cells, the epigenome provides the annotations and footnotes that dictate how our DNA is correctly interpreted. Cellular functions require appropriate transcriptional activation and repression through chemical modifications on DNA and their associated histone proteins. These epigenetic marks modulate various non-coding sequences to establish cell-type specific transcriptional programs. Our research investigates how these molecular mechanisms govern gene expression in development and disease, focusing specifically on repetitive elements and cis-regulatory elements, which comprise roughly half the human genome. These sequences play crucial roles in modulating gene expression. This presentation will detail how such elements influence the epigenome and higher-order chromatin structure in mammalian cells. Through a multi-faceted approach combining epigenomic assays, genome engineering, and cellular and molecular biology techniques, we have identified specific elements that function as regulators of important genes in complex human pathologies. These sequences can affect the recruitment of specific transcription factors, chromatin modifiers, or alter 3D chromatin architecture. Understanding these intricate processes is essential for deciphering the functional roles of repetitive elements in both normal physiology and disease pathogenesis, ultimately paving the way for novel therapeutic interventions targeting epigenetic dysregulation.
