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| Status |
Public on Nov 23, 2010 |
| Title |
GC-rich Sequence Elements Recruit Polycomb Repressive Complex 2 (PRC2) in ES cells |
| Organism |
Mus musculus |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
|
| 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 E. 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.
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| |
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| Overall design |
Analysis of YY1 binding in two cell types
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| |
|
| Contributor(s) |
Mendenhall EM, Bernstein BE |
| Citation(s) |
21170310 |
| |
| Submission date |
Nov 08, 2010 |
| Last update date |
Nov 19, 2022 |
| Contact name |
Kevin Dong |
| Organization name |
Dana-Farber Cancer Institute
|
| Street address |
360 Longwood Ave
|
| City |
Boston |
| State/province |
MASSACHUSETTS |
| ZIP/Postal code |
02215 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL9250 |
Illumina Genome Analyzer II (Mus musculus) |
|
| Samples (2) |
| GSM628031 |
YY1 ChIPSeq in V6.5 murine ES cells |
| GSM628032 |
YY1 ChIPSeq in Neural Progenitor cells |
|
| Relations |
| SRA |
SRP004556 |
| BioProject |
PRJNA134307 |
