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

ABSTRACT: DNA methylation is essential for embryonic development and implicated in the regulation of genomic imprinting. Genomic imprinting is established in the germline through parent-specific methylation of distinct cis-regulatory DNA sequences, called imprinting control regions (ICRs). Which factors bind to the opposing chromatin states at ICRs within the same nuclear environment was not systematically addressed. By using a proximity labelling approach with the methylation sensitive transcription factor ZFP57, we identified ATF7IP and other major components of the epigenetic maintenance machinery at ICRs.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Cell Culture, Embryonic Stem Cell

SUBMITTER: Tuncay Baubec

LAB HEAD: Tuncay Baubec

PROVIDER: PXD034918 | Pride | 2023-03-10

REPOSITORIES: Pride

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

Butz Stefan S Schmolka Nina N Karemaker Ino D ID Villaseñor Rodrigo R Schwarz Isabel I Domcke Silvia S Uijttewaal Esther C H ECH Jude Julian J Lienert Florian F Krebs Arnaud R AR de Wagenaar Nathalie P NP Bao Xue X Zuber Johannes J Elling Ulrich U Schübeler Dirk D Baubec Tuncay T

Nature genetics 20221104 11

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 ide ...[more]

PMID: 36333500

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