Genome anchoring to nuclear landmarks drives functional compartmentalization of the nuclear space.

The spatial organization of the genome contributes to essential functions such as transcription and chromosome integrity maintenance. The principles governing nuclear compartmentalization have been the focus of considerable research over the last decade. In these studies, the genome-nuclear structure interactions emerged as a main driver of this particular 3D genome organization. In this review, we describe the interactions between the genome and four major landmarks of the nucleus: the nuclear lamina, the nuclear pores, the pericentromeric heterochromatin and the nucleolus. We present the recent studies that identify sequences bound to these different locations and address the tethering mechanisms. We give an overview of the relevance of this organization in development and disease. Finally, we discuss the dynamic aspects and self-organizing properties that allow this complex architecture to be inherited.