A dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia [CUT&RUN]
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1064101 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR27506300_1.fastq.gz | Fastqsanger.gz | |||
| SRR27506300_2.fastq.gz | Fastqsanger.gz | |||
| SRR27506301_1.fastq.gz | Fastqsanger.gz | |||
| SRR27506301_2.fastq.gz | Fastqsanger.gz | |||
| SRR27506302_1.fastq.gz | Fastqsanger.gz |
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Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Although intensified therapeutic protocols have improved the outcome of T-ALL patients, they coincide with severe short- and long-term side effects. In addition, no salvage therapeutic strategies are available for primary therapy-resistant or relapsed T-ALL, resulting in a dismal outcome for these patients. It highlights the need to identify new targets in T-ALL biology that allow the development of less toxic targeted therapies. PSIP1, a histone mark reader, is a dependency factor in KMT2A-rearranged myeloid leukemia, but is dispensable for normal hematopoiesis, making it an attractive therapeutic target. Nonetheless, rare recurrent inactivating mutations and deletions of PSIP1, suggest that PSIP1 could act as a tumor suppressor in T-ALL. Here, we demonstrate that the loss of Psip1 accelerates T-ALL initiation in mice and we identified a correlation with reduced H3K27me3 binding. Contrastingly, loss of PSIP1 impaired cell proliferation in several human and murine T-ALL cell lines. In these cell lines, PSIP1 loss leads to a significant downregulation of COX20, an assembly factor of the cytochrome c oxidase in the mitochondria, and is associated with a reduction in mitochondrial respiration. Similarly to what was observed for PSIP1, loss of COX20 expression also leads to an impairment of proliferation in these T-ALL cell lines. These data corroborate that PSIP1 can exert a dual role in the context of T-ALL, either as a tumor suppressor gene during tumor initiation or as a dependency factor in tumor maintenance.
2024-10-20 | GSE253137 | GEO
Project description:A dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia
| PRJNA1064104 | ENA
Project description:A dual role for PSIP1/LEDGF in T-cell acute lymphoblastic leukemia [RNA-seq]
| PRJNA1064102 | ENA
Project description:T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Although intensified therapeutic protocols have improved the outcome of T-ALL patients, they coincide with severe short- and long-term side effects. In addition, no salvage therapeutic strategies are available for primary therapy-resistant or relapsed T-ALL, resulting in a dismal outcome for these patients. It highlights the need to identify new targets in T-ALL biology that allow the development of less toxic targeted therapies. PSIP1, a histone mark reader, is a dependency factor in KMT2A-rearranged myeloid leukemia, but is dispensable for normal hematopoiesis, making it an attractive therapeutic target. Nonetheless, rare recurrent inactivating mutations and deletions of PSIP1, suggest that PSIP1 could act as a tumor suppressor in T-ALL. Here, we demonstrate that the loss of Psip1 accelerates T-ALL initiation in mice and we identified a correlation with reduced H3K27me3 binding. Contrastingly, loss of PSIP1 impaired cell proliferation in several human and murine T-ALL cell lines. In these cell lines, PSIP1 loss leads to a significant downregulation of COX20, an assembly factor of the cytochrome c oxidase in the mitochondria, and is associated with a reduction in mitochondrial respiration. Similarly to what was observed for PSIP1, loss of COX20 expression also leads to an impairment of proliferation in these T-ALL cell lines. These data corroborate that PSIP1 can exert a dual role in the context of T-ALL, either as a tumor suppressor gene during tumor initiation or as a dependency factor in tumor maintenance.
2024-10-20 | GSE253138 | GEO
Project description:The LEDGF transcript from the PSIP1 gene was knocked down in Jurkat cells using RNAi technology. The resulting Jurkat-derived cell line (Jurkat-siJK2) was compared to a control cell line (wild type Jurkat) using microarray analysis. Genes identified as being modulated by LEDGF were preferential targets of HIV integration. Experiment Overall Design: 2 cell lines were used, Jurkat-siJK2 (experimental) and wild-type Jurkat (control). 3 independent cultures of each cell line were used for independent RNA extractions, labeling reactions and array hybridizations.
2008-06-15 | E-GEOD-7508 | biostudies-arrayexpress
Project description:R-loops are transcriptional by-products that pose a persistent threat to genome integrity and are implicated in accelerated ageing and cancer. PSIP1/LEDGF is a multifunctional chromatin protein that associates with transcriptional elongation machinery. Here, we demonstrated that PSIP1 interacts with R-loops generated at the site of transcription and along with the factors involved in R-loop resolution, including PARP1. Reduced PSIP1 levels in human and mouse cells lead to an increase in R-loop levels and DNA damage at the PSIP1 binding sites. This increased R-loops and DNA damage was specific at the RNA polymerase II transcription sites, causing local transcriptional arrest. In addition, we demonstrate that PSIP1 can be targeted for increasing the sensitivity of cancer cells to PARP1 inhibitors and transcription-coupled DNA damaging agents. These findings show the critical role of PSIP1 in reducing the R-loop burden and DNA damage at the transcriptionally active regions of the genome.
2023-12-08 | GSE220233 | GEO
Project description:R-loops are transcriptional by-products that pose a persistent threat to genome integrity and are implicated in accelerated ageing and cancer. PSIP1/LEDGF is a multifunctional chromatin protein that associates with transcriptional elongation machinery. Here, we demonstrated that PSIP1 interacts with R-loops generated at the site of transcription and along with the factors involved in R-loop resolution, including PARP1. Reduced PSIP1 levels in human and mouse cells lead to an increase in R-loop levels and DNA damage at the PSIP1 binding sites. This increased R-loops and DNA damage was specific at the RNA polymerase II transcription sites, causing local transcriptional arrest. In addition, we demonstrate that PSIP1 can be targeted for increasing the sensitivity of cancer cells to PARP1 inhibitors and transcription-coupled DNA damaging agents. These findings show the critical role of PSIP1 in reducing the R-loop burden and DNA damage at the transcriptionally active regions of the genome.
2023-12-08 | GSE220232 | GEO
Project description:R-loops are transcriptional by-products that pose a persistent threat to genome integrity and are implicated in accelerated ageing and cancer. PSIP1/LEDGF is a multifunctional chromatin protein that associates with transcriptional elongation machinery. Here, we demonstrated that PSIP1 interacts with R-loops generated at the site of transcription and along with the factors involved in R-loop resolution, including PARP1. Reduced PSIP1 levels in human and mouse cells lead to an increase in R-loop levels and DNA damage at the PSIP1 binding sites. This increased R-loops and DNA damage was specific at the RNA polymerase II transcription sites, causing local transcriptional arrest. In addition, we demonstrate that PSIP1 can be targeted for increasing the sensitivity of cancer cells to PARP1 inhibitors and transcription-coupled DNA damaging agents. These findings show the critical role of PSIP1 in reducing the R-loop burden and DNA damage at the transcriptionally active regions of the genome.
2023-12-08 | GSE220231 | GEO
Project description:R-loops are transcriptional by-products that pose a persistent threat to genome integrity and are implicated in accelerated ageing and cancer. PSIP1/LEDGF is a multifunctional chromatin protein that associates with transcriptional elongation machinery. Here, we demonstrated that PSIP1 interacts with R-loops generated at the site of transcription and along with the factors involved in R-loop resolution, including PARP1. Reduced PSIP1 levels in human and mouse cells lead to an increase in R-loop levels and DNA damage at the PSIP1 binding sites. This increased R-loops and DNA damage was specific at the RNA polymerase II transcription sites, causing local transcriptional arrest. In addition, we demonstrate that PSIP1 can be targeted for increasing the sensitivity of cancer cells to PARP1 inhibitors and transcription-coupled DNA damaging agents. These findings show the critical role of PSIP1 in reducing the R-loop burden and DNA damage at the transcriptionally active regions of the genome.
2023-12-08 | GSE245788 | GEO
Project description:The p52 isoform of Psip1/Ledgf links histone H3K36 methylation and the regulation of alternative splicing. Chromatin immunoprecipitation (ChIP) of Psip1 together with H3K36me3 and H3K4me3 and by ChIP-on-chip analysis demonstrated that, Like H3K36me3, Psip1 is enriched on exons of highly expressed genes,
2012-04-12 | GSE28153 | GEO