Heterochromatin establishment at pericentromeres depends on nuclear position

Mammalian development begins with fertilization of an oocyte by the sperm followed by genome-wide epigenetic reprogramming. This involves de novo establishment of chromatin domains, including the formation of pericentric heterochromatin. We dissected the spatiotemporal kinetics of the first acquisition of heterochromatic signatures of pericentromeric chromatin and found that the heterochromatic marks follow a temporal order that depends on a specific nuclear localization. We addressed whether nuclear localization of pericentric chromatin is required for silencing by tethering it to the nuclear periphery and show that this results in defective silencing and impaired development. Our results indicate that reprogramming of pericentromeric heterochromatin is functionally linked to its nuclear localization.