Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers

ABSTRACT: Genetic studies have identified common variants within the HBS1L-MYB intergenic region on chromosome 6q associated with elevated fetal hemoglobin (HbF) levels and other clinically important human erythroid traits. The mechanism by which the non-coding sequence variants affect these traits is still not clear. Here we report that several of the variants affect regulatory elements that are occupied by key erythroid transcription factors within this region. These elements interact with MYB, a critical regulator of erythroid development and HbF levels. We show that several of the variants reduce transcription factor binding, affecting long-range interactions with MYB, and MYB expression levels. We provide here a functional explanation for the genetic association of HBS1L-MYB intergenic polymorphisms with human erythroid traits and HbF levels. Our results further designate MYB as a bona fide target for therapeutic induction of HbF to ameliorate sickle cell and β-thalassemia disease severity.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52637 | GEO | 2014/07/24

SECONDARY ACCESSION(S): PRJNA229562

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Similar Datasets

ATF4 regulates MYB to increase g-globin in response to loss of β-globin [ChIP-seq]

Project description:Boontanrart et al model the cellular stress that occurs upon reduction in β-globin in human erythroid cells. Decrease in β-globin attenuates the eIF2aP-ATF4 pathway and results in upregulating fetal -globin. Down-regulation of ATF4 leads to decreased levels of the -globin repressor MYB through direct binding at the HBS1L-MYB intergenic region.

2020-07-26 | GSE153767 | GEO

ATF4 regulates MYB to increase g-globin in response to loss of β-globin [RNA-seq]

Project description:Boontanrart et al model the cellular stress that occurs upon reduction in β-globin in human erythroid cells. Decrease in β-globin attenuates the eIF2aP-ATF4 pathway and results in upregulating fetal g-globin. Down-regulation of ATF4 leads to decreased levels of the g-globin repressor MYB through direct binding at the HBS1L-MYB intergenic region.

2020-07-26 | GSE153764 | GEO

Homo sapiens

Project description:HBS1L-MYB intergenic variants modulate fetal hemoglobin via long-range MYB enhancers

| PRJNA229562 | ENA

RNAi profiling by array of human CD34-derived erythroid progenitors treated with BCL11A siRNAs

Project description:Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders. BCL11A siRNA label: B, NT siRNA label: N Experiment Overall Design: Microarray expression analysis from CD34-derived erythroid progenitors treated with either non-targeting (NT) control siRNAs or BCL11A targeting siRNAs. Six samples from the NT control and six samples from the BCL11A siRNA treatment are included. Cells were harvested on day 7 of erythroid differentiation after introduction of siRNAs on day 0 of the differentiation protocol. Experiment Overall Design: 6 BCL11A siRNA datasets, 6 control (NT) datasets

2009-01-13 | E-GEOD-13284 | biostudies-arrayexpress

Transcription profiling of mouse erythroleukemia (MEL) cells expressing tagged versions of BCL11A

Project description:Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders. Expression clone label: FBB (4 different subclones, with 2 arrays each), Control label: MelBirA Experiment Overall Design: Microarray expression analysis from parental control mouse erythroleukemia (MEL) cells containing the BirA enzyme (MelBirA cells) and cells containing tagged versions (FLAG-Biotag) of BCL11A. Two control datasets and eight datasets from four subclones containing tagged BCL11A are included.

2009-01-13 | E-GEOD-13283 | biostudies-arrayexpress

Human CD34-derived erythroid progenitors treated with BCL11A siRNAs

2008-12-05 | GSE13284 | GEO

Mouse Erythroleukemia (MEL) Cells Expressing Tagged Versions of BCL11A

Project description:Differences in the amount of fetal hemoglobin (HbF) that persists into adulthood affect the severity of sickle cell disease and the beta-thalassemia syndromes. Genetic association studies have identified sequence variants in the gene BCL11A that influence HbF levels. Here we examine BCL11A as a potential regulator of HbF expression. The high HbF BCL11A genotype is associated with reduced BCL11A expression. Moreover, abundant expression of full-length forms of BCL11A is developmentally restricted to adult erythroid cells. Down-regulation of BCL11A expression in primary adult erythroid cells leads to robust HbF expression. Consistent with a direct role of BCL11A in globin gene regulation, we find that BCL11A occupies several discrete sites in the beta-globin gene cluster. BCL11A emerges as a therapeutic target for reactivation of HbF in beta-hemoglobin disorders. Expression clone label: FBB (4 different subclones, with 2 arrays each), Control label: MelBirA Keywords: cell type comparsion

2008-12-05 | GSE13283 | GEO

Expression Profiling of Erythroid Progenitors After MYB shRNA Knockdown

2011-01-03 | GSE25678 | GEO

Expression Profiling of Erythroid Progenitors After MYB shRNA Knockdown

Project description:MYB plays a critical role as a regulator of erythropoieisis. We have shown that MYB silences epsilon and gamma-globin expression in erythroid progenitors. We here examine erythroid cells at the basophilic erythroblast stage of differentiation with MYB shRNA or control lentiviral transduction prior to differentiation. We have cultured CD34 cells and transduced the cells with lentiviruses harboring shRNAs targeting MYB or controls and then allowed the cells to differentiate down the erythroid lineage. At the basophilic erythroblast stage of differentiation, the cells were harvested and total RNA was extracted. This was used to hybridize to Affymetrix expression arrays using the HG-U133 Plus 2.0 platform to ascertain expression differences that occur with the knockdown of MYB.

2011-01-03 | E-GEOD-25678 | biostudies-arrayexpress

MYB silencing in CD34+ progenitor cells

Project description:The c-Myb transcription factor is highly expressed in immature hematopoietic cells and down-regulated during differentiation. To define the role of c-Myb in human hematopoietic lineage commitment, we studied the effects of its silencing during the commitment of human CD34+ Hematopoietic stem/progenitor cells. In CD34+ cells c-Myb silencing determined a cell cycle arrest in G0/G1 phase which strongly decreased the clonogenic efficiency, togheter with a reduction of erythroid colonies coupled with an increase of the macrophage and megakaryocyte ones. Moreover, morphological and flow cytometry data supported the preferential macrophage and megakaryocyte differentiation of c-Myb-silenced CD34+ cells. Taken together our data indicate that c-Myb is essential for the commitment along the erythroid and granulocyte lineages but not for the macrophage and megakaryocyte differentiation. Gene expression profiling of c-Myb-silenced CD34+ cells identified some potential c-Myb targets which can account for these effects, to study by Chromatin Immunoprecipitation and Luciferase Reporter Assay.

2010-07-14 | GSE13110 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

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