Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

KAT7 maintains myeloid leukemogenesis recruits BRD4 to the promoters of target loci to maintain then MLL-AF9 transcriptional programme

ABSTRACT: KAT7 maintains myeloid leukemogenesis recruits BRD4 to the promoters of target loci to maintain then MLL-AF9 transcriptional programme

PROVIDER: PRJNA551672 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR11906476_1.fastq.gz	Fastqsanger.gz
	SRR11906476_2.fastq.gz	Fastqsanger.gz
	SRR11906477_1.fastq.gz	Fastqsanger.gz
	SRR11906477_2.fastq.gz	Fastqsanger.gz
	SRR11906478_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 66

Similar Datasets

KAT7 maintains myeloid leukemogenesis recruits BRD4 to the promoters of target loci to maintain then MLL-AF9 transcriptional programme

Project description:Here we investigate the essentiality of lysine acetyltransferase KAT7 in AMLs driven by the MLL-X fusions. We find that KAT7 activity is required for the recruitment of the MLL-fusion associated adaptor proteins such as BRD4 to gene promoters, which are critical for the maintenance of the MLL-AF9 transcriptional programme. Our findings propose that KAT7 is a plausible therapeutic target for this poor prognosis subtype of AML.

2020-07-27 | GSE133516 | GEO

Histone H3K36me2-specific methyltransferase ASH1L promotes the MLL-AF9-induced leukemogenesis

Project description:ASH1L and MLL1 are two histone methyltransferases that facilitate transcriptional activation during normal development. However, the roles of ASH1L and its enzymatic activity in the development of MLL-rearranged leukemias are not fully elucidated in Ash1L gene knockout animal models. In this study, we used an Ash1L conditional knockout mouse model to show that loss of ASH1L in hematopoietic progenitor cells impaired the initiation of MLL-AF9-induced leukemic transformation in vitro. Furthermore, genetic deletion of ASH1L in the MLL-AF9-transformed cells impaired the maintenance of leukemic cells in vitro and largely blocked the leukemia progression in vivo. Importantly, the loss of ASH1L function in the Ash1L-deleted cells could be rescued by wild-type but not the catalytic-dead mutant ASH1L, suggesting the enzymatic activity of ASH1L was required for its function in promoting MLL-AF9-induced leukemic transformation. At the molecular level, ASH1L enhanced the MLL-AF9 target gene expression by directly binding to the gene promoters and modifying the local histone H3K36me2 levels. Thus, our study revealed the critical functions of ASH1L in promoting the MLL-AF9-induced leukemogenesis, which provides a molecular basis for targeting ASH1L and its enzymatic activity to treat MLL-arranged leukemias.

2021-09-07 | GSE183413 | GEO

Histone H3K36me2-specific methyltransferase ASH1L promotes the MLL-AF9-induced leukemogenesis

Project description:Histone H3K36me2-specific methyltransferase ASH1L promotes the MLL-AF9-induced leukemogenesis

| PRJNA760532 | ENA

RNA-seq identifies expressions changes upon loss of BCoR-AF9 binding

Project description:Purpose: To identify the expression changes responsible for loss of leukemogenesis upon abrogation of BCoR binding to AF9 Methods: Cells were transfected with LentiViral particles containing either WT AF9 or E531R mutants. Cells were allowed to grow for 24 hours and then harvested into TriZol for RNA isolation and sequencing. Results: Loss of BCoR-AF9 results in change in expression of a number of genes involved in the hematopoietic lineage, cell motility and migration, and cell adhesion

2019-12-01 | GSE105767 | GEO

Differential roles of BAF and PBAF subunits, Arid1b and Arid2, in MLL-AF9 leukemogenesis

Project description:Differential roles of BAF and PBAF subunits, Arid1b and Arid2, in MLL-AF9 leukemogenesis

| PRJNA778208 | ENA

RUNX1 isoforms in leukemogenesis

Project description:Aneuploidy and structural aberrations affecting chromosome 21 (Hsa21) are the most frequent in cytogentic events in acute myeloid leukemia. However, it remains unclear why leukemic blasts select for amplifications of Hsa21 or parts of it and why children with Down syndrome (i.e. trisomy 21) are at a high risk of developing leukemia. Here, we propose that disequilibrium of the RUNX1 isoforms and resultant RUNX1A dominance are key to trisomy 21-associated leukemogenesis. Using a Hsa21-focussed CRISPR-Cas9 screen, we uncovered a strong and specific RUNX1 dependency in myeloid leukemia associated with Down syndrome (ML-DS). High levels of RUNX1A – as seen in ML-DS – synergized with the pathognomonic Gata1s mutation in ML-DS pathogenesis, an effect that was reversed upon restoration of the normal RUNX1A:RUNX1C equilibrium. Mechanistically, RUNX1A displaces RUNX1C from its endogenous binding sites and recruits the MYC cofactor MAX to induce oncogenic programs and perturb normal differentiation. This presents a therapeutic vulnerability that can be exploited by interfering with MYC:MAX dimerization. Our study highlights the importance of alternative splicing in leukemogenesis, and paves the way for developing specific and targeted therapies for ML-DS as well as for other leukemias with Hsa21 aneuploidy or RUNX1 isoform disequilibrium.

2023-05-10 | PXD030616 | Pride

Stem cell plasticity, acetylation of H3K14 and de novo gene activation rely on KAT7

Project description:In the conventional model of transcriptional activation, transcription factors bind to response elements and recruit co-factors, including histone acetyltransferases. Contrary to this model, we show that the histone acetyltransferase KAT7 (HBO1/MYST2) is required genome-wide for histone H3 lysine 14 acetylation (H3K14ac). Examining neural stem cells, we found that KAT7 and H3K14ac were present not only at transcribed genes, but also at inactive genes, intergenic regions and in heterochromatin. KAT7 and H3K14ac were not required for the continued transcription of genes that were actively transcribed at the time of loss of KAT7, but indispensable for the activation of repressed genes. The absence of KAT7 abrogated neural stem cell plasticity, diverse differentiation pathways and cerebral cortex development. Reexpression of KAT7 restored stem cell developmental potential. Overexpression of KAT7 enhanced neuron and oligodendrocyte differentiation. Our data suggest that KAT7 prepares chromatin for transcriptional activation and is a prerequisite for gene activation.

2022-12-09 | GSE220602 | GEO

KAT7 promotes malignant phenotypes of colorectal cancer via MRAS-mediated activation of the MAPK/ERK pathway

Project description:Histone acetyltransferases (HATs) play a crucial role in transcriptional regulation by acetylating histones. Dysregulation of HAT activity is implicated in developmental disorders and cancer. In this study, we discovered an upregulated KAT7 signaling pathway in colorectal cancer (CRC) and its association with poor patient survival. Knockdown of KAT7 suppressed CRC cell viability, proliferation, migration, and invasion while promoting apoptosis. Conversely, KAT7 overexpression enhanced these cellular processes. In vivo experiments demonstrated that KAT7 knockdown inhibited CRC growth and lung metastasis. Mechanistically, KAT7 acetylated histone H3 at lysine 14 (H3K14) to enhance MRAS transcription, which activated the MAPK/ERK pathway and promoted tumorigenesis. Overexpression of MRAS or treatment with the ERK activator C6 Ceramide rescued the tumor inhibition caused by KAT7 silencing. The acetyltransferase activity of KAT7 is essential for CRC progression. Reexpression of KAT7, but not KAT7 acetyltransferase activity-deficient mutants, rescued MRAS expression, ERK phosphorylation, and CRC tumorigenesis in KAT7 knockdown CRC cells. Taken together, our results define the essential role of KAT7 in CRC tumorigenesis, rationalizing its potential as a therapeutic target for CRC treatment.

2024-06-27 | GSE270298 | GEO

Increased DNA Methylation of Dnmt3b-Targets Impairs Leukemogenesis (RRBS)

Project description:The de novo DNA methyltransferases Dnmt3a and Dnmt3b are of crucial importance in hematopoietic stem cells, and Dnmt3b has recently been shown to play a role in genic methylation. Forced Dnmt3b expression induced widespread DNA hypermethylation in myc-bcl2 induced leukemias, especially at promoters and gene bodies of stem cell-related genes. MLL-AF9 induced leukemogenesis showed much less pronounced DNA hypermethylation upon Dnmt3b expression. Nonetheless, leukemogenesis was delayed in both models with a shared core set of DNA hypermethylated regions and suppression of stem cell-related genes. Our findings indicate a critical role for Dnmt3b-mediated DNA methylation in leukemia development and maintenance of LSC function. To investigate how Dnmt3b-mediated DNA methylation affects leukemogenesis, we analyzed leukemia development under conditions of high and physiological methylation levels in a tetracycline-inducible knockin mouse model. High expression of Dnmt3b slowed leukemia development in serial transplantations and impaired leukemia stem cell (LSC) function.

2016-01-11 | E-GEOD-71039 | biostudies-arrayexpress

Loss of MBD2 Attenuates MLL-AF9-Driven Leukemogenesis By Reducing Leukemic Cell Cycling via CDKN1C

Project description:Loss of MBD2 Attenuates MLL-AF9-Driven Leukemogenesis By Reducing Leukemic Cell Cycling via CDKN1C

| PRJNA701410 | ENA