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PRC1.6 molecule L3MBTL2 protects MYCN-amplified neuroblastoma cells via epigenetic gene suppression

ABSTRACT: PRC1.6 molecule L3MBTL2 protects MYCN-amplified neuroblastoma cells via epigenetic gene suppression

PROVIDER: PRJNA832099 | ENA |

REPOSITORIES: ENA

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PRC1.6 molecule L3MBTL2 protects MYCN-amplified neuroblastoma cells via epigenetic gene suppression

Project description:Polycomb-group complexes are evolutionarily conserved epigenetic machineries that regulate stem cell fate decisions/development and are also implicated in tumorigenesis mainly by histone modification. PRC1 complexes mediates ubiquitylation of histone H2A on lysine 119 and consists of PRC1.1 to PRC1.6 complexes. Here, we studied the functional roles of a PRC1.6 molecule L3MBTL2 in neuroblastoma (NB) cells. L3MBTL2 knockout- and knockdown-experiments elucidated that L3MBTL2 depletion suppressed NB cell proliferation according with cell cycle arrest and gamma-H2A up-regulation. L3MBTL2 knockout profoundly suppressed xenograft tumor formation. Transcriptome analysis detected the suppressed cell cycle-related pathways and the activated the differentiation-related pathways. The remarkable de-repressed genes by the L3MBTL2 knockout were BRME1 and NRIP3. ChIP experiments showed co-localization of the PRC1.6 components PCGF6/E2F6/L3MBTL2 and MYCN at the transcription start sites (TSS) of these genes. L3MBTL2 knockout reduced H2AK119ub marks at the TSS regions but PCGF6 binding was heterogeneously changed. This study clarified the significance of PRC1.6 molecule L3MBTL2 in NB cell homeostasis and the epigenetic mechanism of the L3MBTL2-mediated gene suppression in NB that regulates the PRC1.6 complex localization and H2AK119 mono-ubiquitination in a gene locus-specific manner.

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The Super Elongation Complex Drives Transcriptional Addiction in MYCN-amplified Neuroblastoma

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Neuroblastoma: MYCN normal vs. MYCN amplified

Project description:To evaluate the expression of genes associated with MYCN in NB, 10 tumors with MYCN amplification and 10 with normal MYCN copy number were subjected to oligonucleotide microarray using Agilent oligo microarray chips. Two-condition experiment, MYCN normal vs. MYCN amplified 10 NB patient tissues for each group.

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To identify transcripts that are differentially expressed in the MYCN amplified vs MYCN non-amplified cell lines using Next Generation Sequencing

Project description:The aims of this study are to compare transcripts that are differentially expressed in the MYCN amplified compare to the MYCN non-amplified neuroblastoma cell lines, in particular, long non-coding RNAs. Methods: Ribosomal depleted RNAs from six human neuroblastoma cell lines were subjected to deep sequencing, using Illumina Hiseq. Results: We identified 459 transcripts are differentially expressed betweeen the MYCN amplified and the MYCN non-amplified cell lines. Conclusions: We have identified a novel long noncoding RNA lncNB1 that is highly expressed in the MYCN amplified compared to the MYCN non-amplified cell lines.

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