Menin is a Targetable Epigenetic Regulator in Glioblastoma (ChIP-Seq)
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1101575 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR28726387_1.fastq.gz | Fastqsanger.gz | |||
| SRR28726387_2.fastq.gz | Fastqsanger.gz | |||
| SRR28726388_1.fastq.gz | Fastqsanger.gz | |||
| SRR28726388_2.fastq.gz | Fastqsanger.gz | |||
| SRR28726389_1.fastq.gz | Fastqsanger.gz |
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Project description:Menin is a Targetable Epigenetic Regulator in Glioblastoma (RNA-Seq)
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Project description:Glioblastomas (GBM) are highly lethal tumors that are refractory to treatment. Here we describe a novel approach to target the epigenetic landscape of GBM and destabilize the glioma progenitor program, leading to inhibition of tumor growth. This is achieved through disruption of the activities of menin, an orphan protein that we demonstrate to play a pro-oncogenic role in GBM. Using pharmacologic and genetic tools, we identify HMGN1, a nucleosome binding chromatin architectural protein as a novel partner for menin. Disruption of this interaction via a newly designed small molecule mimics the major effects of knocking out MEN1, particularly leading to the suppression of H3K27 acetylation marks at genes critical for glioma progenitor identity, as well as promising therapeutic in vivo activity. This work demonstrates a novel role for menin as an epigenetic co-regulator of maintenance and proliferation of glioma.
2025-04-17 | GSE264271 | GEO
Project description:Glioblastomas (GBM) are highly lethal tumors that are refractory to treatment. Here we describe a novel approach to target the epigenetic landscape of GBM and destabilize the glioma progenitor program, leading to inhibition of tumor growth. This is achieved through disruption of the activities of menin, an orphan protein that we demonstrate to play a pro-oncogenic role in GBM. Using pharmacologic and genetic tools, we identify HMGN1, a nucleosome binding chromatin architectural protein as a novel partner for menin. Disruption of this interaction via a newly designed small molecule mimics the major effects of knocking out MEN1, particularly leading to the suppression of H3K27 acetylation marks at genes critical for glioma progenitor identity, as well as promising therapeutic in vivo activity. This work demonstrates a novel role for menin as an epigenetic co-regulator of maintenance and proliferation of glioma.
2025-04-17 | GSE264270 | GEO
Project description:We over-expressed an epigenetic regulator in a glioblastoma (GBM) primary culture from an adult patient. These GBM cells have cancer stem cell phenotypes, as they have self-renewal properties and tumor initiation potential when transplanted in immunocompromised mice. ATAC-seq was performed on cells over-expressing the epigenetic regulator and control cells expressing EGFP. ATAC-Seq on glioblastoma cells that over-express EGFP or an epigenetic regulator.
2015-12-08 | E-GEOD-67633 | biostudies-arrayexpress
Project description:Menin inhibitors that disrupt Menin-MLL interaction hold promise for treating specific acute myeloid leukemia subtypes, including KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncover a potential resistance mechanism independent of canonical Menin-MLL targets. We show that a group of non-canonical Menin targets, which are bivalently co-occupied by active Menin and repressive H2AK119ub marks, are typically downregulated following Menin inhibition. The loss of Polycomb Repressive Complex 1.1 (PRC1.1) subunits, such as PCGF1 or BCOR, leads to Menin inhibitor resistance by epigenetic reactivation of these non-canonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficent leukemia cells to Menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to the BCL2 inhibition, and combinational treatment of venetoclax overcomes the resistance to Menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated non-canonical Menin targets in modulating Menin inhibitor response and provide potential strategies to treat leukemias with compromised PRC1.1 function.
2024-11-20 | GSE249076 | GEO
Project description:Menin inhibitors that disrupt Menin-MLL interaction hold promise for treating specific acute myeloid leukemia subtypes, including KMT2A rearrangements (KMT2A-r), yet resistance remains a challenge. Here, through systematic chromatin-focused CRISPR screens, along with genetic, epigenetic, and pharmacologic studies in a variety of human and mouse KMT2A-r AML models, we uncover a potential resistance mechanism independent of canonical Menin-MLL targets. We show that a group of non-canonical Menin targets, which are bivalently co-occupied by active Menin and repressive H2AK119ub marks, are typically downregulated following Menin inhibition. The loss of Polycomb Repressive Complex 1.1 (PRC1.1) subunits, such as PCGF1 or BCOR, leads to Menin inhibitor resistance by epigenetic reactivation of these non-canonical targets, including MYC. Genetic and pharmacological inhibition of MYC can resensitize PRC1.1-deficent leukemia cells to Menin inhibition. Moreover, we demonstrate that leukemia cells with the loss of PRC1.1 subunits exhibit reduced monocytic gene signatures and are susceptible to the BCL2 inhibition, and combinational treatment of venetoclax overcomes the resistance to Menin inhibition in PRC1.1-deficient leukemia cells. These findings highlight the important roles of PRC1.1 and its regulated non-canonical Menin targets in modulating Menin inhibitor response and provide potential strategies to treat leukemias with compromised PRC1.1 function.
2024-11-20 | GSE249078 | GEO
Project description:METTL7B is an essential epigenetic regulator of lineage specification in glioblastoma
| PRJNA1016411 | ENA
Project description:Multiple endocrine neoplasia type I (MEN1) is a familial cancer syndrome characterized primarily by tumors of multiple endocrine glands. The gene for MEN1 encodes a ubiquitously expressed tumor suppressor protein called menin. Menin was recently shown to interact with several components of a trithorax family histone methyltransferase complex including ASH2, Rbbp5, WDR5, and the leukemia proto-oncoprotein MLL. To elucidate menin's role as a tumor suppressor and gain insights into the endocrine-specific tumor phenotype in MEN1, we mapped the genomic binding sites of menin, MLL1, and Rbbp5, to approximately 20,000 promoters in HeLa S3, HepG2, and pancreatic islet cells using the strategy of chromatin-immunoprecipitation coupled with microarray analysis. We found that menin, MLL1, and Rbbp5 localize to the promoters of thousands of human genes but do not always bind together. These data suggest that menin functions as a general regulator of transcription. Keywords: ChIP/chip NHGRI Menin ChIP-Chip
2006-07-24 | E-GEOD-5357 | biostudies-arrayexpress
Project description:We over-expressed an epigenetic regulator in a glioblastoma (GBM) primary culture from an adult patient. These GBM cells have cancer stem cell phenotypes, as they have self-renewal properties and tumor initiation potential when transplanted in immunocompromised mice. An epigenetic regulator (ER) was over-expressed in the GBM primary culture G514NS. EGFP was expressed from the same vector backbone as a control. N = 3 biological replicates for each of EGFP- and ER-overexpressing cells. Please note that complete data output (with 74,342 data rows) from Partek analysis contains several identifiers which are not represented in the GPL17586, and therefore is linked as Series supplementary file.
2015-11-11 | E-GEOD-63296 | biostudies-arrayexpress
Project description:METTL7B is an essential epigenetic regulator of lineage specification in glioblastoma [DNAme]
| PRJNA1016410 | ENA