ArticleBlood cells, molecules & diseases2010
cJun modulates Ggamma-globin gene expression via an upstream cAMP response element.
Article in Blood cells, molecules & diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it, 26 citations in OpenAlex.
- A systematic review of known mechanisms of hydroxyurea-induced fetal hemoglobin for treatment of sickle cell disease.Expert review of hematology · 2015Pooled it
- Article
- MicroRNA29B induces fetal hemoglobinFrontiers in medicine · 2022Article
- Synthesis and pharmacological evaluation of pomalidomide derivatives useful for sickle cell disease treatment.Bioorganic chemistry · 2021Article
- Stroke in a Child with Hemoglobin SC Disease: A Case Report Describing use of Hydroxyurea after Transfusion Therapy.Pediatric reports · 2017Article
- Original Research: A case-control genome-wide association study identifies genetic modifiers of fetal hemoglobin in sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2016Article
- Hydroxyurea down-regulates BCL11A, KLF-1 and MYB through miRNA-mediated actions to induce γ-globin expression: implications for new therapeutic approaches of sickle cell disease.Clinical and translational medicine · 2016Article
- Cell signaling pathways involved in drug-mediated fetal hemoglobin induction: Strategies to treat sickle cell disease.Experimental biology and medicine (Maywood, N.J.) · 2015Review
- Hydroxyurea-inducible SAR1 gene acts through the Giα/JNK/Jun pathway to regulate γ-globin expression.Blood · 2014Article
- HSF1 protects neurons through a novel trimerization- and HSP-independent mechanism.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2014Article
- Globin gene expression in correlation with G protein-related genes during erythroid differentiation.BMC genomics · 2013Article
- Evaluation of Signaling Pathways Involved in γ-Globin Gene Induction Using Fetal Hemoglobin Inducer Drugs.International journal of hematology-oncology and stem cell research · 2013Review
- Regulation of Gγ-globin gene by ATF2 and its associated proteins through the cAMP-response element.PloS one · 2013Article
- ATF2 - at the crossroad of nuclear and cytosolic functions.Journal of cell science · 2012Article
- Characterization of the transcriptome profiles related to globin gene switching during in vitro erythroid maturation.BMC genomics · 2012Article
- Krüppel-like Factor 4 activates HBG gene expression in primary erythroid cells.British journal of haematology · 2011Article
- Regulation of γ-globin gene expression involves signaling through the p38 MAPK/CREB1 pathway.Blood cells, molecules & diseases · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The upstream Ggamma-globin gene cAMP response element (G-CRE) was previously shown to play a role in drug-mediated fetal hemoglobin induction. This effect is achieved via p38 mitogen activated protein kinase (MAPK)-dependent CREB1 and ATF-2 phosphorylation and G-CRE transactivation. Since this motif is also a predicted consensus binding site for cJun we extended our analysis to determine the ability of cJun to transactivate gamma-globin through the G-CRE. Using chromatin immunoprecipitation assays we showed comparable in vivo cJun and CREB1 binding to the G-CRE region. Protein-protein interactions were confirmed between cJun/ATF-2 and CREB1/ATF-2 but not between CREB1 and cJun. However, we observed cJun and CREB1 binding to the G-CRE in vitro by electrophoretic mobility shift assay. Promoter pull-down assay followed by sequential western blot analysis confirmed co-localization of cJun, CREB1, and ATF-2 on the G-CRE. To show functional relevance, enforced expression studies with pLen-cJun and a Ggamma-promoter (-1500 to +36) luciferase reporter were completed; we observed a concentration-dependent increase in luciferase activity with pLen-cJun similar to that produced by CREB1 enforced expression. Moreover, the G/A mutation at -1225 in the G-CRE abolished cJun transactivation. Finally, enforced cJun expression in K562 cells and normal primary erythroid progenitors enhanced endogenous gamma-globin gene expression. We conclude that these data indicate that cJun activates the Ggamma-globin promoter via the G-CRE in a manner comparable with CREB1 and propose a model for gamma-globin activation based on DNA-protein interactions in the G-CRE.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.