DNA sequence and chromatin modifiers cooperate to confer epigenetic bistability at imprinting control regions.

ABSTRACT: Genomic imprinting is regulated by parental-specific DNA methylation of imprinting control regions (ICRs). Despite an identical DNA sequence, ICRs can exist in two distinct epigenetic states that are memorized throughout unlimited cell divisions and reset during germline formation. Here, we systematically study the genetic and epigenetic determinants of this epigenetic bistability. By iterative integration of ICRs and related DNA sequences to an ectopic location in the mouse genome, we first identify the DNA sequence features required for maintenance of epigenetic states in embryonic stem cells. The autonomous regulatory properties of ICRs further enabled us to create DNA-methylation-sensitive reporters and to screen for key components involved in regulating their epigenetic memory. Beside

SUBMITTER: Butz S 

PROVIDER: S-EPMC7613817 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature