Epigenetics is a major mechanism in human health and disease. Data from a range of diseases (cancer, neurological and immunological disorders) have uncovered altered epigenomes arising from mutations, altered expression and/or copy number alterations of numerous epigenetic factors (histones, DNA and chromatin modifying enzymes, reader proteins, chromatin modulators and noncoding RNAs). Genome-wide analyses have illustrated the relationship between altered epigenetic states (e.g., modified DNA, histones and chromatin packaging) and disease onset and progression. Furthermore, both local and long-range nuclear chromatin architecture are increasingly recognized as major contributors to normal and pathologic epigenetic states. This conference, held jointly with a conference on “3D Genome”, will cover the most current knowledge of epigenetic events modulating nuclear function (gene expression regulation, enhancer modulation, domains and structural organization as well as cell division and differentiation), while relating this to normal and disease models. In addition, this conference will highlight the impact that preclinical and clinical epigenetic therapeutics have on multiple diseases including cancer, immunological and neurological disorders. An interdisciplinary panel of speakers including both thought leaders in the field as well as young investigators will survey the latest research results and conceptual understanding of fundamental mechanisms of epigenetic signaling, especially as they relate to regulation of gene expression programs. Presentations and workshops will highlight the latest technologies and methodologies for studying epigenetic states and 3D chromatin architecture in cells, tissues and organisms.