Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Transcriptional control of HP1a by the RNA binding proteins RBMX/L1 maintain chromatin state in myeloid leukemia

ABSTRACT: RNA binding proteins (RBPs) are key arbiters of post-transcriptional regulation that have been found to be dysregulated in hematological malignancies. Here, we identify the RBP RBMX and its retrogene RBMXL1 to be required for murine and human myeloid leukemogenesis. RBMX/L1 are overexpressed in acute myeloid leukemia (AML) primary patients compared to healthy individuals, and RBMX/L1 loss delayed leukemia development. Complex chromosomal karyotyping analysis and assay for transposase-accessible chromatin sequencing demonstrated that RBMX/L1 loss led to significant changes in chromatin accessibility and compaction. We found that RBMX/L1 directly binds to mRNAs and affects transcription of multiple loci, including the heterochromatin protein 1 alpha (HP1a) mRNA. Using single molecule resolution RNA fluorescence in situ hybridization, we uncovered that RBMX/L1 controls the nascent transcription of the HP1a locus. Forced HP1a expression rescued the RBMX/L1 depletion effects on cell growth and apoptosis. Overall, we determine that RBMX/L1 control leukemia cell survival by regulating chromatin state through its downstream target HP1a. These findings illuminate a novel mechanism for RBPs directly promoting transcription and suggest RBMX/L1 as well as HP1a as potential novel therapeutic targets in myeloid malignancies.

ORGANISM(S): Homo sapiens

PROVIDER: GSE153637 | GEO | 2021/03/18

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

Transcriptional control of HP1a by the RNA binding proteins RBMX/L1 maintain chromatin state in myeloid leukemia

Project description:Transcriptional control of HP1a by the RNA binding proteins RBMX/L1 maintain chromatin state in myeloid leukemia

| PRJNA643547 | ENA

RBMX preferentially associates with repetitive DNAs along with RPA

Project description:To characterize the binding sites of RBMX and RPA on chromatin, 293T cells were treated with CPT and binding profiles were obtained by ChIP-seq assay. RBMX ChIP-seq profile was highly correlated with RPA ChIP-seq profile, both showing strong peaks at centromeres. To characterize the occupancy sites bound by both RBMX and RPA, we annotated their shared peaks. The results showed that these sequences are mostly enriched on repetitive DNAs including rRNA, simple repeats and satellite DNAs.

2019-07-27 | GSE134980 | GEO

Role of RBMX in the post-transcriptional control of homeotic genes

Project description:Wild-type and RBMX-knockdown HEK293 cells where profiled at the transcriptome and translatome levels for the expression of 50 homeotic genes. Targeted RNA-seq libraries were built and sequenced on an Illumina MiSeq machine to allow for accurate gene expression quantification of this specific set of genes. To assess the binding of RBMX to the same set of mRNAs, RNA immunoprecipitation was also performed on HIS-HA tagged RBMX expressing HEK293 cells.

2020-03-04 | GSE118383 | GEO

Translational profiling of RBMX-overexpressed HEK293 cells

Project description:Wild-type and RBMX-overexpressed HEK293 cells where profiled at the transcriptome and translatome levels through polysomal profiling. Paired-end RNA-seq libraries were built and sequenced on an Illumina HiSeq 2000 machine to allow for accurate gene expression quantification and alternative splicing isoforms detection.

2019-12-01 | GSE68990 | GEO

RBMX suppresses tumorigenicity and progression of bladder cancer via interaction with hnRNP A1 protein to regulate PKM alternative splicing

Project description:Bladder cancer (BCa) is one of the most common malignant tumors of urinary system and has high incidence rate and mortality but there is a lack of effective treatment. Therefore, an in-depth study of the molecular mechanisms involved in BCa is of great significance for improving the survival of patients with advanced BCa. We found that the expression of RBMX was significantly declined in BCa, especially in muscle-invasive BCa. BCa patients with low levels of RBMX had poor prognoses. By in vitro and in vivo experiments, RBMX was shown to inhibit BCa cells growth and metastasis. Co-IP coupled with MS and GO analysis identified hnRNP A1 as a RBMX-binding protein. Mechanistically, RBMX competitively bond to the RGG box of hnRNP A1 and antagonized the hnRNP A1-mediated regulation of PKM splicing by blocking the binding of the RGG motif of hnRNP A1 to the sequences flanking PKM exon 9, resulting in downregulation of PKM2 and upregulation of PKM1. By decreasing the PKM2/PKM1 ratio, RBMX suppressed BCa cells aerobic glycolysis, which further inhibited tumorigenicity and progression of BCa.

2020-11-23 | GSE150548 | GEO

RBMX preferentially associates with repetitive DNAs along with RPA

Project description:RBMX preferentially associates with repetitive DNAs along with RPA

| PRJNA556911 | ENA

Gene expression data from NK cells sorted for PD-L1 after co-incubation with K562 myeloid leukemia cells

Project description:The objective was to determine if there are differences in gene expression in PD-L1+ and PD-L1- NK cells after co-incubation of NK cells with target K562 myeloid leukemia cells.

2019-10-18 | GSE132976 | GEO

Search for a novel therapeutic target in myeloid leukemia

Project description:Antibody-based therapy for cancer is now one of the most successful and important strategies for treating patients with hematological malignancies. However, the lack of efficient tumor-associated antigens restricts the targeting therapy of myeloid leukemia. Analysis of the gene expression proï¬les of primary bone marrow samples from human acute myeloid leukemia (AML) patients or healthy donors was to identify and expand novel targets for the treatment of myeloid leukemias. we found that epithelial cell adhesion molecule (EpCAM) is overexpressed in patients with AML. we analyzed the gene expression proï¬les of bone marrow mononuclear cells from 2 human acute myeloid leukemia (AML) patients and 2 healthy donors using an oligonucleotide microarray, to identify up-regulated genes in AML samples comparing with healthy tissues.

2016-05-14 | E-GEOD-79605 | biostudies-arrayexpress

Copy number analysis in de novo and therapy-related myeloproliferative neoplasms

Project description:Loss of chromosome 7 and del(7q) [-7/del(7q)] are recurring cytogenetic abnormalities in hematologic malignancies, including acute myeloid leukemia and therapy-related myeloid neoplasms, and associated with an adverse prognosis. We performed SNP array analysis on de novo and therapy-related myeloid neoplasms and identified a 2.17 Mb commonly deleted segment on chromosome band 7q22.1 containing CUX1, a gene encoding a homeodomain-containing transcription factor. Haploinsufficiency of the highly conserved ortholog, cut, led to hemocyte overgrowth and tumor formation in Drosophila melanogaster. Similarly, haploinsufficiency of CUX1 gave human hematopoietic cells a significant engraftment advantage upon transplantation into immunodeficient mice. These data identify CUX1 as a conserved, haploinsufficient tumor suppressor frequently deleted in myeloid neoplasms. We performed SNP-array analysis of 34 primary patient samples with de novo or therapy-related myeloid leukemia and one acute myeloid leukemia cell line, UoCM1. For patient samples, DNA was obtained from the white blood cells of bone marrow or peripheral blood leukemia specimens. Cytogenetic analysis revealed clonal -7/del(7q) in 17 of the cases.

2012-11-24 | E-GEOD-42482 | biostudies-arrayexpress

Role of RBMX in the post-transcriptional control of homeotic genes

Project description:Role of RBMX in the post-transcriptional control of homeotic genes

| PRJNA485413 | ENA