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Series GSE40860 Query DataSets for GSE40860
Status Public on Dec 26, 2012
Title KDM2B binds CpG islands and modulates recruitment of Ring1b
Organism Mus musculus
Experiment type Genome binding/occupancy profiling by high throughput sequencing
Summary CpG island elements are associated with most mammalian gene promoters, yet how they contribute to gene regulation remains poorly understood. Recently it has become clear that a subset of CpG islands in embryonic stem cells can act as polycomb response elements and are recognized by the polycomb silencing systems to regulate the expression of genes involved in pluripotency and early developmental transcription programs. How CpG islands function mechanistically as nucleation sites for polycomb repressive complexes remains unknown. Here we discover that the KDM2B protein, by virtue of its ZF-CxxC DNA binding domain, specifically recognizes non-methylated DNA in CpG islands elements genome-wide. Through a physical interaction with the polycomb repressive complex 1 (PRC1), KDM2B targets PRC1 to CpG islands where it contributes to H2AK119ub1 and gene repression at a subset of polycomb targets. Unexpectedly, we also find that CpG islands are occupied by low levels of PRC1 throughout the genome, suggesting that the KDM2B-PRC1 complex may sample CpG island associated genes for susceptibility to polycomb mediated silencing. These observations demonstrate an unexpected and direct link between recognition of CpG islands by KDM2B and targeting of the polycomb repressive system. This provides the basis for a new model describing the functionality of CpG islands as mammalian PREs.
Overall design ChIP-Seq to compare KDM2A vs. KDM2B genome-wide binding profiles and to understand the contribution of KDM2B to RING1B nucleation. Binding of Kdm2a and Kdm2b to the genome was examined in wildtype mESC, and Kdm2b and Ring1b in mESC where Kdm2b has been stably knocked down by shRNA.
Contributor(s) Klose RJ, Sudbery IM, Farcas AM
Citation(s) 23256043
Submission date Sep 13, 2012
Last update date May 15, 2019
Contact name Ian Sudbery
Organization name University of Sheffield
Department Molecular Biology and Biotechnology
Lab Sudbery Lab for Computational Genomics
Street address Firth Court, Western Bank
City Sheffield
ZIP/Postal code S11 8HG
Country United Kingdom
Platforms (1)
GPL13112 Illumina HiSeq 2000 (Mus musculus)
Samples (9)
GSM1003593 WT-Kdm2a
GSM1003594 WT-Kdm2b
GSM1003595 WT-Input
This SubSeries is part of SuperSeries:
GSE41267 KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands
BioProject PRJNA175125
SRA SRP015743

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Supplementary file Size Download File type/resource
GSE40860_RAW.tar 3.4 Gb (http)(custom) TAR (of WIG)
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Raw data are available in SRA
Processed data provided as supplementary file

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