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GSE10477
Mus musculus
3 Downloadable Samples
Description
The Polycomb group (PcG) gene products mediate heritable silencing of developmental regulators in metazoans, participating in one of two distinct multimeric protein complexes, the Polycomb repressive complexes-1 (PRC1) and -2 (PRC2)1-5. PRC2 catalyses trimethylation of histone H3 at lysine 27 (H3K27) which in turn is thought to provide a recruitment site for PRC13-7. Recent studies demonstrate that mono-ubiquitylation of histone H2A at lysine 119 is important in PcG mediated silencing with the core PRC1 component Ring1A/B functioning as the E3 ligase8. PRC2 has been shown to share target genes with the core transcription network to maintain embryonic stem (ES) cells including Oct4 and Nanog9. Here we identify an essential role for PRC1 in repressing developmental regulators in ES cells, and thereby in maintaining ES cell pluripotency. A significant proportion of the PRC1 target genes are also repressed by Oct4. We demonstrate that engagement of PRC1 and PRC2 at target genes is Oct4-dependent and moreover that Ring1B interacts with Oct4. Collectively these results show that PcG complexes are instrumental in Oct4-dependent repression required to maintain pluripotency of ES cells. This study provides a first functional link between a core ES cell regulator and global epigenetic regulation of the genome.
Publication Title
Polycomb group proteins Ring1A/B are functionally linked to the core transcriptional regulatory circuitry to maintain ES cell identity.
Sample Metadata Fields
No sample metadata fields
View Samples- Mus musculus
- 23 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 4 Downloadable Samples
Description
Mouse CD34(-)KSL hematopoietic stem cells and CD34(+)KSL multipotent progenitors were purified by cell sorting from bone marrow of 8-week-old C57BL/6 mice, and their gene expression was analyzed.
Publication Title
Forced expression of the histone demethylase Fbxl10 maintains self-renewing hematopoietic stem cells.
Sample Metadata Fields
Specimen part
View Samples- Mus musculus
- 12 Downloadable Samples
Description
Two distinct Polycomb complexes, PRC1 and PRC2, collaborate to maintain epigenetic repression of key developmental loci in embryonic stem cells (ESCs). PRC1 and PRC2 have histone modifying activities, catalyzing mono-ubiquitination of histone H2A (H2AK119u1) and trimethylation of H3 lysine 27 (H3K27me3) respectively. Compared to H3K27me3, localization and role of H2AK119ub1 is not fully understood in ESCs. Here we present genome-wide H2AK119u1 maps in ESCs and identify a group of genes at which H2AK119u1 is deposited in a Ring1-dependent manner. These genes are a distinctive subset of genes with H3K27me3 enrichment and are the central targets of Polycomb silencing that are required to maintain ESC identity. We further show that the H2A ubiquitination activity of PRC1 is dispensable for its target binding and its activity to compact chromatin at Hox loci, but is indispensable for efficient repression of target genes and thereby ESC maintenance. These data demonstrate that multiple effector mechanisms including H2A ubiquitination and chromatin compaction combine to mediate PRC1-dependent repression of genes that are crucial for the maintenance of ESC identity. Utilization of these diverse effector mechanisms might provide a means to maintain a repressive state that is robust yet highly responsive to developmental cues during ES cell self-renewal and differentiation.
Publication Title
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Sample Metadata Fields
Specimen part, Cell line, Treatment
View Samples- Mus musculus
- 12 Downloadable Samples
Description
We used microarrays to investigate the restoration of repression of PRC1 target gene expression in Ring1A/B-dKO ES cells stably expressing either of mock, WT or mutant Ring1B construct.
Publication Title
Histone H2A mono-ubiquitination is a crucial step to mediate PRC1-dependent repression of developmental genes to maintain ES cell identity.
Sample Metadata Fields
Specimen part, Treatment
View Samples- Mus musculus
- 9 Downloadable Samples
Description
This SuperSeries is composed of the SubSeries listed below.
Publication Title
Combined targeting of JAK2 and Bcl-2/Bcl-xL to cure mutant JAK2-driven malignancies and overcome acquired resistance to JAK2 inhibitors.
Sample Metadata Fields
Specimen part, Disease, Disease stage
View Samples