Proteomics approaches to research protein-DNA interactions in human diseases

Abstract

Protein-DNA interactions are essential for the regulation of cellular processes, including gene expression, DNA repair, and replication. Understanding these interactions in the context of human diseases is crucial for identifying potential biomarkers and therapeutic targets. Proteomics has emerged as a powerful tool to investigate protein-DNA interactions at a global scale, enabling the identification of key proteins involved in these processes. This review focuses on various proteomic techniques used to research protein-DNA interactions in human diseases, including chromatin immunoprecipitation (ChIP)-sequencing, affinity purification-mass spectrometry (AP-MS), and cross-linking followed by mass spectrometry (CLMS). These methods provide valuable insights into the molecular mechanisms underlying disease progression, particularly in cancer, neurodegenerative diseases, and autoimmune disorders. The integration of proteomics with next-generation sequencing technologies has greatly enhanced the identification of protein-DNA complexes and their role in disease pathogenesis. This review also discusses the challenges and limitations of current proteomic approaches, such as the need for high-quality samples, the complexity of protein-DNA interaction networks, and the interpretation of large-scale data. Furthermore, the potential of proteomics to uncover novel therapeutic strategies, including the development of small molecules or antibodies that target specific protein-DNA interactions, is explored. Ultimately, a better understanding of protein-DNA interactions in human diseases will pave the way for the development of more effective diagnostic and therapeutic tools. The future of proteomics in disease research lies in the integration of multi-omics data and the application of advanced computational tools to unravel the complexity of protein-DNA interactions.