Our work focuses on the formation and regulation of chromatin domains and their ultimate roles in the nucleus. We are particularly interested in the mechanisms of heterochromatin establishment and function. Heterochromatin operates in organisms from yeast to humans to determine cell identity and maintain genome stability by silencing genes. Because heterochromatin functions in such central processes, misregulation of this genomic structure can have dire consequences such as cancer or abnormal development. Our work investigates the mechanisms by which silencing is carried out. We use a combination of in vitro assembly of chromatin domains, mechanistic biochemistry, proteomic analysis, and genome-wide chromatin profiling to understand the complex superstructural “neighborhoods” of chromosomes.