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Regulation of Gamma globin gene expression by AT2 and its associated proteins through the cAMP response element.

ABSTRACT: The upstream Gg-globin cAMP-response element (G-CRE) plays a role in regulating Gg-globin expression through binding of CREB1, cJun and ATF2. In this study we identified the ATF2 DNA-binding partners. ATF2 knockdown resulted in a significant reduction of g-globin expression accompanied by decreased ATF2 binding to the G-CRE. By contrast, stably expressed ATF2 in K562 cells increased g-globin, which was reduced by ATF2 knockdown. Moreover, a similar role for ATF2 on g-globin expression was observed in primary erythroid progenitors. To understand the role of ATF2 in g-globin expression, chromatographically purified G-CRE/ATF2-interacting proteins were subjected to mass spectrometry analysis; binding partners included CREB1, cJun, Brg1, and histone deacetylases among others. Co-immunoprecipitation and chromatin immunoprecipitation assay demonstrated interaction of these proteins with ATF2 in CD34+ cells undergoing erythroid differentiation which was correlated with g-globin expression during development. These results suggest synergism between developmental stage-specific recruitments of the ATF2 protein complex and expression of g-globin during erythropoiesis. Microarray studies in K562 cells support additional roles for ATF2 in hematopoiesis and chromatin remodeling

ORGANISM(S): Homo sapiens

PROVIDER: GSE50165 | GEO | 2013/10/24

SECONDARY ACCESSION(S): PRJNA216932

REPOSITORIES: GEO

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Regulation of Gamma globin gene expression by AT2 and its associated proteins through the cAMP response element.

Project description:The upstream Gg-globin cAMP-response element (G-CRE) plays a role in regulating Gg-globin expression through binding of CREB1, cJun and ATF2. In this study we identified the ATF2 DNA-binding partners. ATF2 knockdown resulted in a significant reduction of g-globin expression accompanied by decreased ATF2 binding to the G-CRE. By contrast, stably expressed ATF2 in K562 cells increased g-globin, which was reduced by ATF2 knockdown. Moreover, a similar role for ATF2 on g-globin expression was observed in primary erythroid progenitors. To understand the role of ATF2 in g-globin expression, chromatographically purified G-CRE/ATF2-interacting proteins were subjected to mass spectrometry analysis; binding partners included CREB1, cJun, Brg1, and histone deacetylases among others. Co-immunoprecipitation and chromatin immunoprecipitation assay demonstrated interaction of these proteins with ATF2 in CD34+ cells undergoing erythroid differentiation which was correlated with g-globin expression during development. These results suggest synergism between developmental stage-specific recruitments of the ATF2 protein complex and expression of g-globin during erythropoiesis. Microarray studies in K562 cells support additional roles for ATF2 in hematopoiesis and chromatin remodeling Total RNA was isolated from K562 cells in culture following transfection with scrambled siRNA or ATF2 siRNA following which RNA was isolated and gene expression monitored

2013-10-24 | E-GEOD-50165 | biostudies-arrayexpress

bZIP dimers CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun prefer binding some DNA sequences containing 5-formylcytosine and 5-carboxylcytosine

Project description:In mammalian cells, 5-methylcytosine (5mC) occurs in genomic double-stranded DNA (dsDNA) and is enzymatically oxidized to 5-hydroxymethylcytosine (5hmC), then to 5-formylcytosine (5fC), and finally to 5-carboxylcytosine (5caC). These cytosine modifications are enriched in regulatory regions of the genome. The effect of these oxidative products on five bZIP dimers (CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun) binding to five types of dsDNA was measured using protein binding microarrays. The five dsDNAs contain either cytosine in both DNA strands or cytosine in one strand and either 5mC, 5hmC, 5fC, or 5caC in the second strand. Some sequences containing the CEBP half-site GCAA are bound more strongly by all five bZIP domains when dsDNA contains 5mC, 5hmC, or 5fC. dsDNA containing 5caC in some TRE (AP-1)-like sequences, e.g., TGACTAA, is better bound by Zta, ATF3|cJun, and cFos|cJun.

2020-11-16 | GSE141050 | GEO

bZIP dimers CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun prefer binding some DNA sequences containing 5-formylcytosine and 5-carboxylcytosine

Project description:bZIP dimers CREB1, ATF2, Zta, ATF3|cJun, and cFos|cJun prefer binding some DNA sequences containing 5-formylcytosine and 5-carboxylcytosine

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Expression analysis of ZBP-89 deficient human primary erythroid progenitors

Project description:The molecular mechanisms underlying erythroid-specific gene regulation remain incompletely understood. Closely spaced binding sites for GATA, NF-E2/maf and CACCC interacting transcription factors play functionally important roles in globin and other erythroid-specific gene expression. We and others recently identified the CACCC-binding transcription factor ZBP-89 as a novel GATA-1 and NF-E2/mafK interacting partner. Here, we examined the role of ZBP-89 in human globin gene regulation and erythroid maturation using a primary CD34+ cell ex vivo differentiation system. We show that ZBP-89 protein levels rise dramatically during human erythroid differentiation, and that ZBP-89 occupies key cis-regulatory elements within the globin and other erythroid gene loci. ZBP-89 binding correlates strongly with RNA Pol II occupancy, active histone marks, and high-level gene expression. ZBP-89 physically associates with the histone acetyltransferases (HATs) p300 and Gcn5/Trrap, and occupies common sites with Gcn5 within the human globin loci. Lentiviral shRNA knockdown of ZBP-89 results in reduced Gcn5 occupancy, decreased acetylated histone 3 levels, lower globin and erythroid-specific gene expression, and impaired erythroid maturation. Addition of the HDAC inhibitor valproic acid partially reverses the reduced globin gene expression. These findings reveal an activating role for ZBP-89 in human globin gene regulation and erythroid differentiation. Keywords: Human primary erythroid progenitors Expression data of human erythroid progenitors transduced with lentivirus expressing short hairpins against ZBP-89 and control empty vector

2011-08-01 | E-GEOD-31092 | biostudies-arrayexpress

GABPα and CREB1 binding to double nucleotide polymorphisms of their consensus motifs and cooperative binding to the ETS-CRE motif (ACCGGAAGTGACGTCA).

Project description:Previously, cooperative binding to DNA between the bZIP domain of CREB1 and the ETS domain of GABPα was observed for the composite ETS-CRE motif (A0C1C2G3G4A5A6G7T8G9A10C11G12T13C14A15). Single nucleotide polymorphisms (SNPs) at the beginning and end of the ETS motif (ACCGGAAGT) increased cooperative binding. Here, we use a microarray containing all double nucleotide polymorphisms (DNPs) of the ETS-CRE motif to explore GABPα and CREB1 binding to their canonical motifs and their cooperative binding to the ETS-CRE motif. For GABPα, binding to SNPs predicted binding the DNPs. In contrast, CREB1 binding to DNPs showed cooperativity. Similar results were observed for other ETS and bZIP family members. Cooperative binding between GABPα and CREB1 was typically weaker than expected except for DNPs containing A7 and SNPs at the beginning of the ETS motif.

2020-01-01 | GSE125613 | GEO

Expression data from BCL11A-null and wild-type bone marrow erythroid pregenitors

Project description:BCL11A is a critical mediator of hemoglobin switching and gamma-globin silencing. In this study, we showed the BCL11A is required in vivo for developmental silencing of gamma-globin genes in adult animals. We used microarray to determine the changes in gene expression profile after loss of BCL11A in adult erythroid cells CD71+Ter119+ erythroid progenitor cells were FACS-sorted from bone marrows of 6-week old control (Bcl11a +/+) and BCL11A knockout (Bcl11a fl/fl EpoR-Cre+) mice.

2012-03-22 | E-GEOD-28333 | biostudies-arrayexpress

The pivotal and universal role of BGLT3 lncRNA in fetal globin gene expression

Project description:A highly selective and non-genotoxic G9a inhibitor, RK-701 was discovered, which upregulated the mRNA level of γ-globin but not β-globin both in human erythroid cells and in mice. Using RK-701, we examined the induction of the fetal (γ-) globin protein in human erythroid cells; HUDEP-2 and human CD34+ bone marrow and peripheral blood cells.

2023-03-11 | PXD033536 | Pride

Expression analysis of ZBP-89 deficient human primary erythroid progenitors

2011-08-02 | GSE31092 | GEO

SOX6 interacting proteins' identification in K562 cells for the regulation of γ-globin gene expression research

Project description:Human fetal γ-globin gene is developmentally silenced around the birth, and reactivation of γ-globin gene in adulthood sheds new light on ameliorating symptoms of hemoglobin disorders, such as sickle cell disease (SCD) and β-thalassemias. However, the precise regulation process of γ-globin remains incompletely understood. Here, we found that a new protein directly interacted with SOX6 and exerted a significant repression effect on the expression of γ-globin gene in erythroid cells. Further studies have demonstrated that it bound directly to γ-globin gene promoter via octamer binding motif, which in turn suppressed the transcriptional activity of γ-globin gene promoter. Thus, these data indicate that this new protein acts as a novel transcriptional repressor in the regulation of γ-globin gene expression through direct promoter binding, implying a potential alternative therapeutic target for the treatment of SCD and β-thalassemias.

2022-02-16 | PXD024259 | Pride

ChIP-chip from ex-vivo differentiated erythroblasts derived from human primary CD34+ cells

2011-07-30 | GSE31036 | GEO

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