Ontology highlight
ABSTRACT:
PROVIDER: PRJNA819114 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR18458551_1.fastq.gz | Fastqsanger.gz | |||
| SRR18458551_2.fastq.gz | Fastqsanger.gz | |||
| SRR18458552_1.fastq.gz | Fastqsanger.gz | |||
| SRR18458552_2.fastq.gz | Fastqsanger.gz | |||
| SRR18458553_1.fastq.gz | Fastqsanger.gz |
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Project description:The histone methyltransferase Setd8 represses Gata2 expression and regulates erythroid maturation
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Project description:The chromatin modifying enzymes that drive the erythroid-specific transcription program are incompletely understood. Setd8 is the sole histone methyltransferase in mammals capable of generating mono-methylated histone H4 lysine 20 (H4K20me1) and is expressed at significantly higher levels in erythroid cells than any other cell- or tissue- type, suggesting that Setd8 has an erythroid-specific function. To test this hypothesis, stable knockdown of Setd8 was established in extensively self-renewing erythroblasts (ESREs), a well-characterized, non-transformed, model of erythroid maturation. Setd8 knockdown impaired erythroid maturation, characterized by a delay in hemoglobin accumulation, larger cell area, persistent kit expression, incomplete nuclear condensation, and lower rates of enucleation than control cells. Setd8 knockdown did not alter ESRE proliferation or viability, or result in accumulation of DNA damage. Global gene expression analyses following Setd8 knockdown suggests that in erythroid cells, Setd8 functions primarily as a repressor and demonstrated high levels of Gata2 expression. Setd8 occupies critical regulatory elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1 and gain of H4 acetylation at the Gata2 1S promoter. Taken together, these results imply that Setd8 is an important regulator of erythroid maturation that works in part through repression of Gata2. RNA-seq was performed of Setd8 knockdown and control cells, both while the cells were proliferating, and after 6 hours of maturation.
2015-04-24 | E-GEOD-62647 | biostudies-arrayexpress
Project description:SETD8 is a histone methyltransferase that catalyzes the monomethylation of histone H4K20. Overexpressed in cancer, several studies have suggested that it could be a potential target for treatment in certain tumors. However, there are currently very few SETD8 inhibitors, and all of them have bad pharmacological properties. Based on previously published structures of SETD8 bound to an H4K20me peptide, we have discovered a new chemical series of SETD8 inhibitors. As part of the characterization of these molecules, we conducted Thermal Proteome Profiling, aiming to discover potential additional targets as well as a better understanding of the signaling pathways that are affected by the drug.
2024-10-17 | PXD051199 | Pride
Project description:Cellular senescence is an ireversible growth arrest with alterd metabolic potentials including DNA, RNA and protein dynamics. We found that loss of the SETD8/PR-Set7 methyltransferase, which catalyzes mono-methylation of histone H4 at lysine 20 (H4K20me1), induces senescence in human fibroblasts. To investigate the role of SETD8 in cellular senescence, we performed a microarray-based transcriptomic analysis in SETD8-knockdown cells. Our results demonstrate that SETD8 links the epigenomic gene regulation to senescence-associated metabolic remodeling.
2017-03-30 | GSE86545 | GEO
Project description:The chromatin modifying enzymes that drive the erythroid-specific transcription program are incompletely understood. Setd8 is the sole histone methyltransferase in mammals capable of generating mono-methylated histone H4 lysine 20 (H4K20me1) and is expressed at significantly higher levels in erythroid cells than any other cell- or tissue- type, suggesting that Setd8 has an erythroid-specific function. To test this hypothesis, stable knockdown of Setd8 was established in extensively self-renewing erythroblasts (ESREs), a well-characterized, non-transformed, model of erythroid maturation. Setd8 knockdown impaired erythroid maturation, characterized by a delay in hemoglobin accumulation, larger cell area, persistent kit expression, incomplete nuclear condensation, and lower rates of enucleation than control cells. Setd8 knockdown did not alter ESRE proliferation or viability, or result in accumulation of DNA damage. Global gene expression analyses following Setd8 knockdown suggests that in erythroid cells, Setd8 functions primarily as a repressor and demonstrated high levels of Gata2 expression. Setd8 occupies critical regulatory elements in the Gata2 locus, and knockdown of Setd8 resulted in loss of H4K20me1 and gain of H4 acetylation at the Gata2 1S promoter. Taken together, these results imply that Setd8 is an important regulator of erythroid maturation that works in part through repression of Gata2.
2015-04-24 | GSE62647 | GEO
Project description:SETD8 is the sole methyltransferase capable of mono-methylating histone H4, lysine 20. SETD8 is highly expressed in erythroid cells and erythroid deletion of Setd8 is embryonic lethal by embryonic day 11.5 (E11.5) due to profound anemia, suggesting it has an erythroid-specific function. To gain insights into the function of SETD8 during erythroid differentiation, we performed ATAC-seq on sorted populations of E10.5 Setd8 null and control erythroblasts. Accessibility profiles were integrated with expression changes and a mark of heterochromatin (H3K27me3) performed in wild type E10.5 erythroblasts to further understand the role of SETD8 in erythropoiesis. Data integration identified regions of greater chromatin accessibility in Setd8 null cells that co-located with H3K27me3 in wild type E10.5 erythroblasts suggesting that these regions, and their associated genes, are repressed during normal erythropoiesis. Pathway analysis of genes identified through data integration revealed stemness-related pathways. Among those genes were multiple transcriptional regulators active in multipotent progenitors but repressed during erythroid differentiation including Hhex, Hlx, and Gata2. Consistent with a role for SETD8 in erythroid specification, SETD8 expression is upregulated upon erythroid commitment, and Setd8 disruption impairs erythroid colony forming ability. Taken together, our results suggest that Setd8 is important for the establishment of appropriate patterns of gene expression during erythroid differentiation.
2020-03-01 | GSE138106 | GEO
Project description:Functional analysis of histone methyltransferase SETD8 in endometrial cancer
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Project description:Epigenetic modulation of herpes simplex virus (HSV) immediate early (IE) genes is a critical regulatory parameter governing lytic infection, latency, and viral reactivation. Multiple factors, including epigenetic complexes associated with the cellular transcriptional coactivator HCF-1, modulate the state of HSV-1 chromatin. As an approach to identify novel epigenetic factors that regulate the initial stage of HSV-1 infection, an epigenetic chemical probe library was screened for their impact on viral IE gene expression. This screen identified several epigenetic inhibitors that modulated IE expression. Notably, UNC0379, an inhibitor of the histone H4K20 mono-methyltransferase SETD8, potently repressed HSV-1 infection in vitro and in vivo. Furthermore, SETD8 inhibition suppressed HSV-1 reactivation in a mouse ganglia explant model. Importantly, these results correlated with enhanced heterochromatin suppression and decreased accessibility of HSV-1 chromatin. Reduced IE transcription was concomitant with disruption in recruitment of HCF-1 and RNA polymerase II (RNAPII). These results are consistent with the established roles of SETD8 in promoting chromatin accessibility through H4K20me1 deposition and regulating transcriptional elongation, suggesting that SETD8 may facilitate multiple steps in regulation of HSV-1 IE gene expression.
2025-11-10 | GSE302607 | GEO
Project description:Epigenetic modulation of herpes simplex virus (HSV) immediate early (IE) genes is a critical regulatory parameter governing lytic infection, latency, and viral reactivation. Multiple factors, including epigenetic complexes associated with the cellular transcriptional coactivator HCF-1, modulate the state of HSV-1 chromatin. As an approach to identify novel epigenetic factors that regulate the initial stage of HSV-1 infection, an epigenetic chemical probe library was screened for their impact on viral IE gene expression. This screen identified several epigenetic inhibitors that modulated IE expression. Notably, UNC0379, an inhibitor of the histone H4K20 mono-methyltransferase SETD8, potently repressed HSV-1 infection in vitro and in vivo. Furthermore, SETD8 inhibition suppressed HSV-1 reactivation in a mouse ganglia explant model. Importantly, these results correlated with enhanced heterochromatin suppression and decreased accessibility of HSV-1 chromatin. Reduced IE transcription was concomitant with disruption in recruitment of HCF-1 and RNA polymerase II (RNAPII). These results are consistent with the established roles of SETD8 in promoting chromatin accessibility through H4K20me1 deposition and regulating transcriptional elongation, suggesting that SETD8 may facilitate multiple steps in regulation of HSV-1 IE gene expression.
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Project description:Leukemic stem cells (LSCs) are at least partially responsible for relapse and resistance in patients with t(8;21) acute myeloid leukemia (AML), while the intricate regulatory network governing LSC stemness is yet to be fully elucidated. Chromatin accessibility remodeled by epigenetic alterations represents a defining hallmark of LSCs, endowing them with enhanced survival and self-renewal capacities, which may offer potential therapeutic opportunities for intervention. Here, we show that SETD8, a lysine methyltransferase that monomethylates lysine 20 of histone H4 (H4K20me1), is essential for the maintenance of stemness in t(8;21) AML LSCs. Genetic deletion or pharmacological inhibition of SETD8 impairs the survival and self-renewal of LSCs in retroviral AML1-ETO9a-driven t(8;21) AML mice and primary t(8;21) AML CD34+ cells. Mechanistically, SETD8 promotes the expression of Ras homolog family member T1 (RHOT1), a mitochondrial outer membrane protein, by increasing chromatin accessibility at the enhancer region, thereby reprogramming mitochondrial homeostasis. These findings improve our understanding of the gene regulation through chromatin accessibility remodeling and establish a link between histone lysine methylation and mitochondrial homeostasis, suggesting a potential strategy for eliminating LSCs in t(8;21) AML.
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