Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1270723 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33781783_1.fastq.gz | Fastqsanger.gz | |||
| SRR33781783_2.fastq.gz | Fastqsanger.gz | |||
| SRR33781784_1.fastq.gz | Fastqsanger.gz | |||
| SRR33781784_2.fastq.gz | Fastqsanger.gz | |||
| SRR33781785_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Nuclear receptor binding SET domain protein 1 (NSD1) is recurrently mutated in human cancers including acute leukemia. We found that NSD1 knockdown altered erythroid clonogenic growth of human CD34+ hematopoietic cells. Ablation of Nsd1 in the hematopoietic system induced a transplantable erythroleukemia in mice. Despite abundant expression of the transcriptional master regulator GATA1, in vitro differentiation of Nsd1-/- erythroblasts was majorly impaired associated with reduced activation of GATA1-induced targets, while GATA1-repressed target genes were less affected. Retroviral expression of wildtype Nsd1, but not a catalytically-inactive Nsd1N1918Q SET-domain mutant induced terminal maturation of Nsd1-/- erythroblasts. Despite similar GATA1 levels, exogenous Nsd1 but not Nsd1N1918Q significantly increased GATA1 chromatin occupancy and target gene activation. Notably, Nsd1 expression reduced the association of GATA1 with the co-repressor SKI, and knockdown of SKI induced differentiation of Nsd1-/- erythroblasts. Collectively, we identified the NSD1 methyltransferase as a novel regulator of GATA1-controlled erythroid differentiation and leukemogenesis.
2020-04-08 | PXD017657 | Pride
Project description:The formation of the mammalian neocortex during development requires coordinated establishment of functional regions at proper anterior-posterior and medial-lateral positions – area patterning, as well as neocortical layers. Although key transcription factors (TFs) were known to specify and maintain cell fates, mechanisms underlying how TFs are precise expressed and repressed are largely elusive. Here we showed that NSD1, the methyltransferase for histone H3 lysine 36 dimethylation (H3K36me2), controls both areal and layer identities of the neocortex. Nsd1-ablated neocortex showed prominent areal shift of all four primary functional regions and aberrant wiring of major cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning and coordination, reminiscent of patients with the Sotos syndrome carrying NSD1 mutations. Although projection neurons (PN) of neocortical layers were mostly properly produced and positioned upon Nsd1 deletion, post-mitotic PNs could not establish their layer-specific identities. More strikingly, in adult Nsd1 conditional knockout neocortices, superficial-layer PNs progressively mis-expressed markers for deep-layer PNs. Moreover, neocortical PNs ablated with Nsd1 remained immature morphologically and electrophysiologically. Loss of NSD1 in post-mitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Our findings revealed that H3K36me2 mediated by NSD1 is required for establishment and maintenance of region- and layer-specific neocortical identities.
2024-01-18 | GSE229338 | GEO
Project description:The formation of the mammalian neocortex during development requires coordinated establishment of functional regions at proper anterior-posterior and medial-lateral positions – area patterning, as well as neocortical layers. Although key transcription factors (TFs) were known to specify and maintain cell fates, mechanisms underlying how TFs are precise expressed and repressed are largely elusive. Here we showed that NSD1, the methyltransferase for histone H3 lysine 36 dimethylation (H3K36me2), controls both areal and layer identities of the neocortex. Nsd1-ablated neocortex showed prominent areal shift of all four primary functional regions and aberrant wiring of major cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning and coordination, reminiscent of patients with the Sotos syndrome carrying NSD1 mutations. Although projection neurons (PN) of neocortical layers were mostly properly produced and positioned upon Nsd1 deletion, post-mitotic PNs could not establish their layer-specific identities. More strikingly, in adult Nsd1 conditional knockout neocortices, superficial-layer PNs progressively mis-expressed markers for deep-layer PNs. Moreover, neocortical PNs ablated with Nsd1 remained immature morphologically and electrophysiologically. Loss of NSD1 in post-mitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Our findings revealed that H3K36me2 mediated by NSD1 is required for establishment and maintenance of region- and layer-specific neocortical identities.
2024-01-18 | GSE229340 | GEO
Project description:The formation of the mammalian neocortex during development requires coordinated establishment of functional regions at proper anterior-posterior and medial-lateral positions – area patterning, as well as neocortical layers. Although key transcription factors (TFs) were known to specify and maintain cell fates, mechanisms underlying how TFs are precise expressed and repressed are largely elusive. Here we showed that NSD1, the methyltransferase for histone H3 lysine 36 dimethylation (H3K36me2), controls both areal and layer identities of the neocortex. Nsd1-ablated neocortex showed prominent areal shift of all four primary functional regions and aberrant wiring of major cortico-thalamic-cortical projections. Nsd1 conditional knockout mice displayed defects in spatial memory, motor learning and coordination, reminiscent of patients with the Sotos syndrome carrying NSD1 mutations. Although projection neurons (PN) of neocortical layers were mostly properly produced and positioned upon Nsd1 deletion, post-mitotic PNs could not establish their layer-specific identities. More strikingly, in adult Nsd1 conditional knockout neocortices, superficial-layer PNs progressively mis-expressed markers for deep-layer PNs. Moreover, neocortical PNs ablated with Nsd1 remained immature morphologically and electrophysiologically. Loss of NSD1 in post-mitotic PNs causes genome-wide loss of H3K36me2 and re-distribution of DNA methylation, which accounts for diminished expression of neocortical layer specifiers but ectopic expression of non-neural genes. Our findings revealed that H3K36me2 mediated by NSD1 is required for establishment and maintenance of region- and layer-specific neocortical identities.
2024-01-18 | GSE229337 | GEO
Project description:Nuclear receptor-binding SET domain protein 1 (NSD1) prototype is a family of mammalian histone methyltransferases (NSD1, NSD2/MMSET/WHSC1, NSD3/WHSC1L1) that are essential in development and are mutated in human acute myeloid leukemia (AML), overgrowth syndromes, multiple myeloma and lung cancers. In AML, the recurring t(5;11)(q35;p15.5) translocation fuses NSD1 to nucleoporin-98 (NUP98). Here, we present the first characterization of the transforming properties and molecular mechanisms of NUP98-NSD1. We demonstrate that NUP98-NSD1 induces AML in vivo, sustains self-renewal of myeloid stem cells in vitro, and enforces expression of the HoxA7, HoxA9, HoxA10 and Meis1 proto-oncogenes. Mechanistically, NUP98-NSD1 binds genomic elements adjacent to HoxA7 and HoxA9, maintains histone H3 Lys 36 (H3K36) methylation and histone acetylation, and prevents EZH2-mediated transcriptional repression of the Hox-A locus during differentiation. Deletion of the NUP98 FG-repeat domain, or mutations in NSD1 that inactivate the H3K36 methyltransferase activity or that prevent binding of NUP98-NSD1 to the Hox-A locus precluded both Hox-A gene activation and myeloid progenitor immortalization. We propose that NUP98-NSD1 prevents EZH2-mediated repression of Hox-A locus genes by colocalizing H3K36 methylation and histone acetylation at regulatory DNA elements. This report is the first to link deregulated H3K36 methylation to tumorigenesis and to link NSD1 to transcriptional regulation of the Hox-A locus. Experiment Overall Design: Total RNA was extracted from stably transformed progenitors cultured in vitro and the expression levels of mRNA transcripts quantified using the Affymetrix GeneChip Mouse Genome 430 2.0 array, as previously described. The GEO database accession numbers: for progenitors immortalized by HoxA9 (GSM190542, GSM190546, GSM190547); for progenitors immortalized by coexpressed HoxA9 plus Meis1 (GSM190548, GSM190549, GSM190550); for progenitors immortalized by NUP98-NSD1 (GSM190551, GSM190552, GSM190553); and for progenitors immortalized by MLL-ENL (GSM190554). Experiment Overall Design: NOTE: CEL files and dChip data were requested by GEO but not provided.
2008-06-11 | E-GEOD-10071 | biostudies-arrayexpress
Project description:Epigenetics, especially histone marks, functions beyond the DNA sequences to regulate gene expression. Depletion of NSD1, which catalyzes H3K36me2, led to both up- and down-regulation of gene expression, indicating NSD1 is associated with both active and repressed gene expression. It’s known that NSD1 regulates the deposition and expansion of H3K27me3, a repressive mark for gene expression, to keep active gene transcription. However, how NSD1 functions to repress gene expression is largely unknown. Here, we found that, when NSD1 was knocked out in mouse embryonic stem cells (mESCs), H3K27ac increased correlatively with the decrease of H3K36me2 at active enhancers, which is associated with mesoderm differentiation genes, leading to elevated gene expression. Mechanistically, NSD1 recruits HDAC1, the deacetylase of H3K27ac, to chromatin. Moreover, HDAC1 knockout (KO) recapitulates the increase of H3K27ac at active enhancers as the NSD1 depletion. Together, we propose that NSD1 deposits H3K36me2 and recruits HDAC1 at active enhancers to serve as a ‘safeguard’, preventing further activation of active enhancer-associated genes.
2021-06-15 | GSE169049 | GEO
Project description:To investigate the changes in gene expression during the process of differentiation into neutrophils and to evaluate the effect of Ak2 hetero-knockout in the process, microarray analysis was performed. HL-60 Ak2 hetero-knockout clone #47 cells were cultured with all-trans retinoic acid (ATRA) for 4 days. The cells were collected at four different time points and total RNA was prepared for use as a sample for microarray analysis.
2022-12-28 | GSE200825 | GEO
Project description:To investigate the changes in gene expression during the process of differentiation into neutrophils and to evaluate the effect of Ak2 hetero-knockout in the process, microarray analysis was performed. HL-60 Ak2 hetero-knockout clone #5 cells were cultured with all-trans retinoic acid (ATRA) for 4 days. The cells were collected at four different time points and total RNA was prepared for use as a sample for microarray analysis.
2022-12-28 | GSE200824 | GEO
Project description:NUP98-NSD1 is one of the most recurring nucleoporin 98 (NUP98) fusions in acute myeloid leukemia (AML). NUP98-NSD1 AML is associated with adverse outcomes and poor response to conventional treatments. However, limited studies have been done to identify new potential targets to develop better treatment approaches. The C-type lectin domain family 12, member A (CLEC12A) is a cell surface receptor that is differentially expressed in leukemic stem cells (LSCs) compared to healthy hematopoietic stem cells (HSCs). We demonstrated a strong overexpression of CLEC12A in both NUP98-NSD1 patients and NUP98-NSD1 transformed murine cells. To understand the role of Clec12a in NUP98-NSD1 AML, we depleted Clec12a expression in NUP98-NSD1+NRASG12D immortalized cells using 3 different sgRNAs targeting 3 different exons. We observed an efficient gene editing in all target sites. NUP98-NSD1+NRASG12D/Clec12a knockout cells showed higher apoptosis and lower colony numbers in vitro compared to NUP98-NSD1+NRASG12D/Clec12a wildtype cells. Importantly, the deletion of Clec12a significantly reduced the leukemic engraftment and prolonged the survival of the NUP98-NSD1+NRASG12D murine model. Our data suggest to further explore CLEC12A as a potential target for the treatment of NUP98-NSD1 AML.
2025-05-14 | GSE282047 | GEO
Project description:mRNA-seq analyses for the differentially expressed genes (DEGs) between Parkinsons's disease patient (holding Lin28 R192G hetero mutation)-iPSC (Pt-iPSC) derived neural stem cell vs Lin28 R192G hetero mutation corrected-iPSC (Corrected Pt-iPSC) derived neural stem cell. To gain further molecular insight into the observed Lin28R192G mutation in Parkinsons's disease (PD) patient iPSC-derived neural stem cell (NSC) functions, we performed mRNA-sequencing (RNA-seq) analysis of the PD patient (holding Lin28 R192G hetero mutation)-iPSC (Pt-iPSC) derived NSC and Lin28 R192G hetero mutation corrected-iPSC (Corrected Pt-iPSC) derived NSC.
2019-08-20 | GSE135995 | GEO