GC-rich sequence elements recruit PRC2 in mammalian ES cells

Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). Ho...

Full description

Saved in:
Bibliographic Details
Published in:PLoS genetics 2010-12, Vol.6 (12), p.e1001244-e1001244
Main Authors: Mendenhall, Eric M, Koche, Richard P, Truong, Thanh, Zhou, Vicky W, Issac, Biju, Chi, Andrew S, Ku, Manching, Bernstein, Bradley E
Format: Article
Language:English
Subjects:
Animals
Cell Differentiation
Deoxyribonucleic acid
Developmental Biology/Cell Differentiation
Developmental Biology/Stem Cells
DNA
DNA binding proteins
DNA methylation
Drosophila
Embryonic stem cells
Embryonic Stem Cells - cytology
Embryonic Stem Cells - metabolism
Escherichia coli
GC Rich Sequence
Genetic aspects
Genetics and Genomics/Epigenetics
Genetics and Genomics/Gene Expression
Genomes
Humans
Mammals - genetics
Mammals - metabolism
Medical research
Mice
Molecular Biology/Chromatin Structure
Molecular Biology/Histone Modification
Nucleotide sequence
Physiological aspects
Polycomb-Group Proteins
Protein Binding
Proteins
Repressor Proteins - genetics
Repressor Proteins - metabolism
Stem cells
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Polycomb proteins are epigenetic regulators that localize to developmental loci in the early embryo where they mediate lineage-specific gene repression. In Drosophila, these repressors are recruited to sequence elements by DNA binding proteins associated with Polycomb repressive complex 2 (PRC2). However, the sequences that recruit PRC2 in mammalian cells have remained obscure. To address this, we integrated a series of engineered bacterial artificial chromosomes into embryonic stem (ES) cells and examined their chromatin. We found that a 44 kb region corresponding to the Zfpm2 locus initiates de novo recruitment of PRC2. We then pinpointed a CpG island within this locus as both necessary and sufficient for PRC2 recruitment. Based on this causal demonstration and prior genomic analyses, we hypothesized that large GC-rich elements depleted of activating transcription factor motifs mediate PRC2 recruitment in mammals. We validated this model in two ways. First, we showed that a constitutively active CpG island is able to recruit PRC2 after excision of a cluster of activating motifs. Second, we showed that two 1 kb sequence intervals from the Escherichia coli genome with GC-contents comparable to a mammalian CpG island are both capable of recruiting PRC2 when integrated into the ES cell genome. Our findings demonstrate a causal role for GC-rich sequences in PRC2 recruitment and implicate a specific subset of CpG islands depleted of activating motifs as instrumental for the initial localization of this key regulator in mammalian genomes.
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1001244