Establishing, maintaining, and removing histone post-translational modifications associated with heterochromatin is critical for shaping genomic structure and function as a cell navigates different stages of development, activity, and disease. Dynamic regulation of the repressive chromatin landscape has been documented in several key cell states — germline cells, activated immune cells, actively replicating, and quiescent cells — with notable variations in underlying mechanisms. Here, we discuss the role of cell states of these diverse contexts in directing and maintaining observed chromatin landscapes. These investigations reveal heterochromatin architectures that are highly responsive to the functional context of a cell's existence and, in turn, their contribution to the cell's stable identity.

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