Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

41 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia [HTS]

ABSTRACT: The plasma cell transcription factor XBP1 is critical for terminal differentiation of B cells into plasma cells but has no known role at earlier stages of B-cell development. Here we show that XBP1 is not only important during early B-cell development and for survival of pre-B cells but also protects pre-B ALL cells. Among pre-B ALL subset, XBP1 was hypomethylated and highest expressed in the Ph+ ALL subset. Cre-mediated deletion of XBP1 in a mouse model of Ph+ ALL compromised proliferation and viability and prolonged survival of leukemia-bearing mice. Interestingly, XBP1 expression levels were positively transcriptionally regulated by STAT5 and negatively by BACH2 and BCL6. High XBP1 expression in high risk ALL patients at the time of diagnosis predicted poor outcome in two clinical trials. Clinically, small-molecule inhibition of IRE1-dependent XBP1-activation caused cell death of patient-derived pre-B ALL cells and affected leukemia-initiation in transplant recipient mice. Collectively, these studies identify XBP1 as an important survival factor and as a potential therapeutic target to overcome drug-resistance in pre-B ALL. Genome-wide profiling of mRNA levels in p210 transduced murine Xbp1 fl/+ pre-B cells with ERT2 (XE.1,2,3) and Cre- ERT2 M-BM- (XC.1,2,3).

ORGANISM(S): Mus musculus

SUBMITTER: Huimin Geng

PROVIDER: E-GEOD-53683 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia

Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series

2014-04-24 | E-GEOD-53685 | biostudies-arrayexpress

A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia [array]

Project description:The plasma cell transcription factor XBP1 is critical for terminal differentiation of B cells into plasma cells but has no known role at earlier stages of B-cell development. Here we show that XBP1 is not only important during early B-cell development and for survival of pre-B cells but also protects pre-B ALL cells. Among pre-B ALL subset, XBP1 was hypomethylated and highest expressed in the Ph+ ALL subset. Cre-mediated deletion of XBP1 in a mouse model of Ph+ ALL compromised proliferation and viability and prolonged survival of leukemia-bearing mice. Interestingly, XBP1 expression levels were positively transcriptionally regulated by STAT5 and negatively by BACH2 and BCL6. High XBP1 expression in high risk ALL patients at the time of diagnosis predicted poor outcome in two clinical trials. Clinically, small-molecule inhibition of IRE1-dependent XBP1-activation caused cell death of patient-derived pre-B ALL cells and affected leukemia-initiation in transplant recipient mice. Collectively, these studies identify XBP1 as an important survival factor and as a potential therapeutic target to overcome drug-resistance in pre-B ALL. Genome-wide profiling of mRNA levels in BCR-ABL1 transduced murine Grp78 fl/fl pre-B cells with an empty vector (Grp78 wild type, MIG-1,2,3) and Cre (Grp78 deletion, CRE-1,2,3).

2014-04-24 | E-GEOD-53684 | biostudies-arrayexpress

Widespread contribution of transposable elements to the innovation of gene regulatory networks [human ENCODE]

Project description:Transposable elements (TE) have been shown to contrain functional transcription factor (TF) binding sites for long, but the extent to which TEs contribute TF binding sites is not well know. Here, we comprehensively mapped binding sites for 26 pairs of orthologous TFs, in two pairs of human and mouse cell lines (i.e., leukemia, and lymphoblast), along with epigenomic profiles representing DNA methylation and six histone modifications. We found that on average, 20% of TF binding sites were embedded in TEs. We further identified 710 TF-TE relationships in which certain TE subfamilies enriched for TF binidng sites. TE-derived TF binding peaks were also strongly associated with decreased DNA methylation and increased enhancer-associated histone marks. Most of the TE-derived TF binding sites were species-specific, but we also identified conserved binding sites. Additionally, 66% of TE-derived TF binding events were cell-type specific, associated with cell-type specific epigenetic landscape. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf To evaluate the contribution of transposable elements (TE) to transcription factor (TF) binding landscapes, we profiled ChIP-seq datasets for 26 TFs in two cell lines in human and mouse, generated by the ENCODE and MouseENCODE consortia. The epigenomic profiles were evaluated from six histone modification in each of the cell lines, also generated by the consortia. We added DNA methylation to the epigenomic profiles, using two complementary techniques, MeDIP-seq and MRE-seq. The mouse data related to this study are available through GSE57230: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE57230

2014-05-09 | E-GEOD-56774 | biostudies-arrayexpress

Widespread contribution of transposable elements to the innovation of gene regulatory networks [mouse ENCODE]

Project description:Transposable elements (TE) have been shown to contrain functional transcription factor (TF) binding sites for long, but the extent to which TEs contribute TF binding sites is not well know. Here, we comprehensively mapped binding sites for 26 pairs of orthologous TFs, in two pairs of human and mouse cell lines (i.e., leukemia, and lymphoblast), along with epigenomic profiles representing DNA methylation and six histone modifications. We found that on average, 20% of TF binding sites were embedded in TEs. We further identified 710 TF-TE relationships in which certain TE subfamilies enriched for TF binidng sites. TE-derived TF binding peaks were also strongly associated with decreased DNA methylation and increased enhancer-associated histone marks. Most of the TE-derived TF binding sites were species-specific, but we also identified conserved binding sites. Additionally, 66% of TE-derived TF binding events were cell-type specific, associated with cell-type specific epigenetic landscape. For data usage terms and conditions, please refer to http://www.genome.gov/27528022 and http://www.genome.gov/Pages/Research/ENCODE/ENCODEDataReleasePolicyFinal2008.pdf To evaluate the contribution of transposable elements (TE) to transcription factor (TF) binding landscapes, we profiled ChIP-seq datasets for 26 TFs in two cell lines in human and mouse, generated by the ENCODE and MouseENCODE consortia. The epigenomic profiles were evaluated from six histone modification in each of the cell lines, also generated by the consortia. We added DNA methylation to the epigenomic profiles, using two complementary techniques, MeDIP-seq and MRE-seq. The human data related to this study are available through GSE56774: http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE56774

2014-05-09 | E-GEOD-57230 | biostudies-arrayexpress

Expression data from two breast cancer cell lines

Project description:During cancer progression, carcinoma cells encounter a variety of cytotoxic stresses such as hypoxia, nutrient deprivation, and low pH as a result of inadequate vascularization. To maintain survival and growth in the face of these physiologic stressors, a set of adaptive response pathways are induced. One adaptive pathway well studied in other contexts is the unfolded protein response (UPR), of which XBP1 is an important component. We used microarrays to detect transcriptome profile changes after XBP1 knockdown in breast cancer cell lines, and identify genes and pathways regulated by XBP1, which could help elucidate how XBP1 mediates the adaptive response of breast cancer to cytotoxic stresses. We extracted RNA and hybridized it to Affymetrix microarrays in two breast cancer cell lines (T47D and MDA-MB-231) under treated (hypoxia and glucose deprivation) or untreated conditions with XBP1 knockdown or not.

2013-09-26 | E-GEOD-49953 | biostudies-arrayexpress

A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia [array]

2014-04-24 | GSE53684 | GEO

A mechanistic rationale for targeting the unfolded protein response in pre-B acute lymphoblastic leukemia [HTS]

2014-04-24 | GSE53683 | GEO

Expression data comparing EBF1 versus Pax5 induced genes

Project description:We used microarrays to establish whether EBF1 and Pax5 repress similar or unique genes. We found that EBF1 uniquely represses the expression of the T-lineage transcription factor Gata3. Ebf1-/- pre-pro-B cells were transduced with either control MigR1, MigY-EBF1 or MigR-Pax5 viruses. 24 hours later, RNA was isolated and processed for Affymetrix microarray analysis. Cells expressing EBF1, Pax5, or neither were sorted and processed. Scale represents log2 value of normalized signal level.

2013-04-12 | E-GEOD-46004 | biostudies-arrayexpress

The IRE1a-XBP1 pathway promotes T helper cell differentiation by resolving secretory stress and accelerating proliferation (ChIP-seq)

Project description:The IRE1a-XBP1 pathway, a conserved adaptive response to the unfolded protein response, is indispensable for development of the secretory cells. It maintains endoplasmic reticulum homeostasis by enhancing protein folding and the secretory capacity of the cells. Here, we used a modified ChIP-seq protocol (ChIPmentation) to investigate the genome-wide binding events of the transcription factor XBP1 in differentiated mouse Th2 cells.

2018-10-06 | E-MTAB-6327 | biostudies-arrayexpress

Genome-wide identification and characterization of functional neuronal activity-dependent enhancers

Project description:Experience-dependent gene transcription is required for nervous system development and function. However, the DNA regulatory elements that control this program of gene expression are not well defined. Here we characterize the enhancers that function across the genome to mediate activity-dependent transcription in neurons. While ~12,000 putative activity-regulated enhancer sequences have previously been identified that are enriched for H3K4me1 and the histone acetyltransferase CBP, we find that this chromatin signature is not sufficient to distinguish which of these regulatory sequences are actively engaged in promoting activity-dependent transcription. We show here that a subset of H3K4me1/CBP positive enhancers that is enriched for H3K27 acetylation (H3K27ac) in vivo, and shows increased H3K27ac upon membrane depolarization of cortical neurons, function to regulate activity-dependent transcription. The function of many of these activity-regulated enhancers appears to be dependent on the binding of FOS, a protein that had previously been thought to interact primarily with the promoters of activity-regulated genes. Furthermore, many of these target genes in cortical neurons encode neuron specific proteins that regulate synaptic development and function. These findings suggest that FOS functions at enhancers to control activity-dependent gene programs that are critical for nervous system function, and provide a resource of activity-dependent enhancers that may give insight into genetic variation that contributes to brain development and disease. Genome-wide maps of H3K27ac and AP1 transcription factors (CFOS, FOSB, JUNB) before and after neuronal activity in mouse cortical neurons.

2014-09-07 | E-GEOD-60192 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data