Dynamic spreading of chromatin-mediated gene silencing and reactivation between neighboring genes in single cells.

ABSTRACT: In mammalian cells genes that are in close proximity can be transcriptionally coupled: silencing or activating one gene can affect its neighbors. Understanding these dynamics is important for natural processes, such as heterochromatin spreading during development and aging, and when designing synthetic gene regulation circuits. Here, we systematically dissect this process in single cells by recruiting and releasing repressive chromatin regulators at dual-gene synthetic reporters, and measuring how fast gene silencing and reactivation spread as a function of intergenic distance and configuration of insulator elements. We find that silencing by KRAB, associated with histone methylation, spreads between two genes within hours, with a time delay that increases with distance. This fast KRAB-med

SUBMITTER: Lensch S 

PROVIDER: S-EPMC9183234 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature