Occupancy profiling of HAND2, MEIS2 and TCF4 by CUT&Tag from Neuroblastoma cells
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ABSTRACT:
PROVIDER: PRJNA981072 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24855900_1.fastq.gz | Fastqsanger.gz | |||
| SRR24855900_2.fastq.gz | Fastqsanger.gz | |||
| SRR24855901_1.fastq.gz | Fastqsanger.gz | |||
| SRR24855901_2.fastq.gz | Fastqsanger.gz | |||
| SRR24855902_1.fastq.gz | Fastqsanger.gz |
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Project description:HAND2, MEIS2 and TCF4 are master transcription factors (TFs) in neuroblastoma and create an interconnected core regulatory circuitry (CRC) by directly occupying each other's and their own super-enhancers (SEs), which leads to high levels of each TF expression inside the CRC. Additionally, CRC TFs cooperatively co-occupy the same SE components, which promotes the expression of genes involved in cell identity and cell-type-specific activities. Super-enhancer-mediated CRC enriched at key oncogenes in neuroblastoma. In the present study, CUT&Tag (Cleavage Under Targets and Tagmentation) analysis was performed to explore the target of HAND2, MEIS2 and TCF4 in NB cells.
2024-05-06 | GSE234337 | GEO
Project description:MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis. Affymetrix microarray assays were performed according to the manufacturer's directions on total RNA isolated from three independent samples of BE(2)-C cells infected with lentiviruses expressing either shGFP or shMEIS2-43 for 48 hours.
2015-03-01 | E-GEOD-56003 | biostudies-arrayexpress
Project description:ChIP-Sequencing on Meis2-HA in E12.5 palate, to identify Meis2 binding chromatin regions and target genes. Haploinsufficiency of MEIS2 is associated with cleft palate in humans and Meis2 inactivation leads to abnormal palate development in mice, implicating an essential role for Meis2 in palate development. However, its functional mechanisms remain unknown. In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis discovered that the Meis2-bound regions possess highly enriched binding motifs of several key osteogenic transcription factors particularly Shox2. Comparison of Meis2 and Shox2 ChIP-seq analyses further revealed a genome-wide co-occupancy, in addition to their co-localization in the developing palate and physical interaction, suggesting that Shox2 and Meis2 act as partners. However, while Shox2 is required for proper palatal bone formation and is a direct downstream target of Meis2, Shox2 overexpression failed to rescue the palatal bone defects in Meis2 mutant background. These results, together with the facts that Meis2 expression is associated with high osteogenic potential and is required for the chromatin accessibility of osteogenic genes, support a vital function of Meis2 in setting up the ground state for palatal osteogenesis.
2020-03-23 | GSE143911 | GEO
Project description:MEIS2 has an important role in development and organogenesis, and is implicated in the pathogenesis of human cancer. The molecular basis of MEIS2 action in tumorigenesis is not clear. Here, we show that MEIS2 is highly expressed in human neuroblastoma cell lines and is required for neuroblastoma cell survival and proliferation. Depletion of MEIS2 in neuroblastoma cells leads to M phase arrest and mitotic catastrophe, whereas ectopic expression of MEIS2 markedly enhances neuroblastoma cell proliferation, anchorage-independent growth, and tumorigenicity. Gene expression profiling reveals an essential role of MEIS2 in maintaining the expression of a large number of late cell cycle genes, including those required for DNA replication, G2-M checkpoint control and M phase progression. Importantly, we identify MEIS2 as a transcription activator of the MuvB-BMYB-FOXM1 complex that functions as a master regulator of mitotic gene expression. Further, we show that FOXM1 is a direct target gene of MEIS2 and is required for MEIS2 to upregulate mitotic genes. These findings link a development gene to the control of cell cycle progression and suggest that high MEIS2 expression is a molecular mechanism for high expression of mitotic genes that is commonly observed in cancers of poor prognosis.
2015-03-01 | GSE56003 | GEO
Project description:We use RNA-sequencing to profile the different expression genes in the palatal mesenchyme of wildtype and Wnt1Cre;Meis2f/f mice at E12.5. Haploinsufficiency of MEIS2 is associated with cleft palate in humans and Meis2 inactivation leads to abnormal palate development in mice, implicating an essential role for Meis2 in palate development. However, its functional mechanisms remain unknown. In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis discovered that the Meis2-bound regions possess highly enriched binding motifs of several key osteogenic transcription factors particularly Shox2. Comparison of Meis2 and Shox2 ChIP-seq analyses further revealed a genome-wide co-occupancy, in addition to their co-localization in the developing palate and physical interaction, suggesting that Shox2 and Meis2 act as partners. However, while Shox2 is required for proper palatal bone formation and is a direct downstream target of Meis2, Shox2 overexpression failed to rescue the palatal bone defects in Meis2 mutant background. These results, together with the facts that Meis2 expression is associated with high osteogenic potential and is required for the chromatin accessibility of osteogenic genes, support a vital function of Meis2 in setting up the ground state for palatal osteogenesis.
2020-03-23 | GSE143912 | GEO
Project description:We use ATAC-seq to identify chromatin accessibility in the palatal mesenchyme of wildtype and Wnt1Cre;Meis2f/f mice at E12.5. Haploinsufficiency of MEIS2 is associated with cleft palate in humans and Meis2 inactivation leads to abnormal palate development in mice, implicating an essential role for Meis2 in palate development. However, its functional mechanisms remain unknown. In this study, we found widespread Meis2 expression in the developing palate in mice. Meis2 inactivation by Wnt1Cre in cranial neural crest cells led to the cleft of the secondary palate. Importantly, about half of Wnt1Cre;Meis2f/f mice exhibited submucous cleft, providing an excellent model for studying palatal bone formation and patterning. Consistent with a complete absence of the palatal bones, integrative analyses of Meis2 ChIP-seq, RNA-seq, and ATAC-seq results identified key osteogenic genes that are regulated directly by Meis2, indicating the fundamental role of Meis2 in palatal osteogenesis. De novo motif analysis discovered that the Meis2-bound regions possess highly enriched binding motifs of several key osteogenic transcription factors particularly Shox2. Comparison of Meis2 and Shox2 ChIP-seq analyses further revealed a genome-wide co-occupancy, in addition to their co-localization in the developing palate and physical interaction, suggesting that Shox2 and Meis2 act as partners. However, while Shox2 is required for proper palatal bone formation and is a direct downstream target of Meis2, Shox2 overexpression failed to rescue the palatal bone defects in Meis2 mutant background. These results, together with the facts that Meis2 expression is associated with high osteogenic potential and is required for the chromatin accessibility of osteogenic genes, support a vital function of Meis2 in setting up the ground state for palatal osteogenesis.
2020-03-23 | GSE143910 | GEO
Project description:Calpains are non-lysosomal, Ca2+-dependent cysteine proteases, which are associated with various cellular functions but have so far been mainly studied in the context of disease. Their contribution to homeostasis in the healthy organism is still not well understood and their substrates have remained enigmatic in most cases. In the present study, we describe a previously unrecognized role for the calpain protease calpain2 in the regulation of neuronal differentiation of adult neural stem- and progenitor cells through cleavage and elimintation of the neuronal fate determinant MEIS2. Mass spectrometry analysis was performed on immunoprecipitated MEIS2 protein to identify phosphory¬lated residues in MEIS2 and on immunoprecipitated MEIS2 incubated with native porcine calpain2 to map calpain2-induced cleavage sites in the protein.
2024-02-08 | PXD036442 | Pride
Project description:HAND2 regulates regional chromation modification [HAND2-knockdown_histone_ChIPseq]
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Project description:Purpose:To identity genomic loci where MEIS2 binds at E14.5 in the LGE Methords: The CUT&Tag assay was performed using E14.5 LGEs dissected from wild-type CD1 mice and a MEIS2 mouse polyclonal antibody as described previously. Results: We derived a set of 13992 loci based on the presence of significant enrichment in MEIS2 libraries and no enrichment in the negative control datasets
2021-08-06 | GSE181192 | GEO
Project description:Surprisingly few pathways signal between cells, raising questions about mechanisms for tissue-specific responses. In particular, Wnt ligands signal in many mammalian tissues, including the intestinal epithelium, where constitutive signaling causes cancer. Genome-wide analysis of DNA cis-regulatory regions bound by the intestine-restricted transcription factor CDX2 in colonic cells uncovered highly significant over-representation of sequences that bind TCF4, a transcriptional effector of intestinal Wnt signaling. Chromatin immunoprecipitation confirmed TCF4 occupancy at most such sites and co-occupancy of CDX2 and TCF4 across short distances. A region spanning the single nucleotide polymorphism rs6983267, which lies within a MYC enhancer and confers colorectal cancer risk in humans, represented one of many co-occupied sites. Co-occupancy correlated with intestine-specific gene expression and CDX2 loss reduced TCF4 binding.These results implicate CDX2 in directing TCF4 binding in intestinal cells. Co-occupancy of regulatory regions by signal-effector and tissue-restricted transcription factors may represent a general mechanism for ubiquitous signaling pathways to achieve tissue-specific outcomes.
2010-08-11 | GSE22572 | GEO