GC-rich sequence elements recruit PRC2 in mammalian ES cells

Area of Science:

• Epigenetics
• Developmental Biology
• Genomics

Background:

• Polycomb proteins are key epigenetic regulators controlling gene expression during development.
• In Drosophila, DNA-binding proteins recruit Polycomb repressive complex 2 (PRC2) to specific DNA sequences.
• The mammalian sequences responsible for PRC2 recruitment have not been identified.

Purpose of the Study:

• To identify the DNA sequences that mediate the de novo recruitment of PRC2 in mammalian embryonic stem cells.
• To elucidate the sequence characteristics that enable PRC2 localization to developmental loci.

Main Methods:

• Integration of engineered bacterial artificial chromosomes into mouse embryonic stem cells.
• Chromatin analysis to assess PRC2 localization.
• Functional assays involving sequence deletion and heterologous DNA integration.

Main Results:

• A 44 kb region of the Zfpm2 locus was found to recruit PRC2.
• A specific CpG island within the Zfpm2 locus was identified as necessary and sufficient for PRC2 recruitment.
• GC-rich sequences, even from bacterial genomes, could recruit PRC2 when depleted of activating transcription factor motifs.

Conclusions:

• GC-rich sequences, specifically CpG islands lacking activating motifs, play a critical role in mammalian PRC2 recruitment.
• These findings reveal a mechanism for the initial localization of PRC2 to developmental genes in mammals.
• This identifies a subset of CpG islands as key players in initiating epigenetic gene repression.