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Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE67552 | GEO | 2016/10/21

SECONDARY ACCESSION(S): PRJNA280228

REPOSITORIES: GEO

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Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2016-10-21 | E-GEOD-67552 | biostudies-arrayexpress

Maintenance of leukemic cell identity by the activity of the Polycomb complex PRC1 in mice.

Project description:Leukemia is a complex heterogeneous disease often driven by the expression of oncogenic fusion proteins with different molecular and biochemical properties. Whereas several fusion proteins induce leukemogenesis by activating Hox gene expression (Hox-activating fusions), others impinge on different pathways that do not involve the activation of Hox genes (non-Hox-activating fusions). It has been postulated that one of the main oncogenic properties of the HOXA9 transcription factor is its ability to control the expression of the p16/p19 tumor suppressor locus (Cdkn2a), thereby compensating Polycomb-mediated repression, which is dispensable for leukemias induced by Hox-activating fusions. We show, by genetically depleting the H2A ubiquitin ligase subunits of the Polycomb repressive complex 1 (PRC1), Ring1a and Ring1b, that Hoxa9 activation cannot repress Cdkn2a expression in the absence of PRC1 and its dependent deposition of H2AK119 monoubiquitination (H2AK119Ub). This demonstrates the essential role of PRC1 activity in supporting the oncogenic potential of Hox-activating fusion proteins. By combining genetic tools with genome-wide location and transcription analyses, we further show that PRC1 activity is required for the leukemogenic potential of both Hox-activating and non-Hox-activating fusions, thus preventing the differentiation of leukemic cells independently of the expression of the Cdkn2a locus. Overall, our results genetically demonstrate that PRC1 activity and the deposition of H2AK119Ub are critical factors that maintain the undifferentiated identity of cancer cells, positively sustaining the progression of different types of leukemia.

| S-EPMC5055382 | biostudies-literature

Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (RNA-seq)

Project description:These data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Total RNA extracted from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.

2016-10-21 | E-GEOD-67517 | biostudies-arrayexpress

Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (ChIP-seq)

Project description:These data include the genome wide occupancy of H2AUbq by ChIP sequencing in Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa. Immuno-precipitation of formaldehyde cross-linked chromatin prepared from Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa using H2AK119Ubq antibody.

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Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (RNA-seq)

Project description:These data include RNA Seq data generated from Ring1b wild type and Ring1b KO Ring1a-/- Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.

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Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (ChIP-seq)

Project description:These data include the genome wide occupancy of H2AUbq by ChIP sequencing in Cdkn2a-/- Lin- HSC cells non-transduced or transduced with MLL-AF9, HOXA9 and PML-RARa.

2016-10-21 | GSE67498 | GEO

Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (RNA-seq_2)

Project description:These data include RNA Seq data generated from wild type and Ring1a Ring1b dKO Cdkn2a-/- MLL-AF9 Leukemic cells

2016-10-21 | GSE85328 | GEO

Maintenance of Leukemic Cell Identity by the Activity of the Polycomb Complex PRC1 (ChIP-seq_2)

Project description:These data include the genome wide occupancy of H2AUbq and H3K27me3 by ChIP sequencing in Ring1a-/-;Ring1bf/f Cdkn2a-/- MLL-AF9 leukemic cells treated with OHT or EtOH

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KDM2B links the Polycomb Repressive Complex 1 (PRC1) to recognition of CpG islands

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

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Variant PRC1 complex dependent H2A ubiquitylation drives PRC2 recruitment and polycomb domain formation

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-05-27 | E-GEOD-55698 | biostudies-arrayexpress