Many human diseases are often caused by abnormal gene expression. In human cells, gene expression is tightly regulated by many large macromolecular complexes, such as coactivators, chromatin remodeling complexes, and long non-coding RNA molecules (IncRNAs). Studying their structures and molecular mechanisms is necessary for understanding how these complexes work and how gene regulation is controlled. Recent development in cryo-electron microscopy (cryo-EM) has already made it possible to determine the structure of the macromolecular complex at near-atomic resolution. We combine the advanced cryo-EM techniques with various biochemical and biophysical approaches to explore the structures and functions of macromolecular assemblies involved in gene regulation.