Regulation of Gγ-Globin Gene By ATF2 and Its Associated Proteins through the Camp-Response Element

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dc.contributor.authorLiu, Lien_US
dc.contributor.authorKarmakar, Subhradipen_US
dc.contributor.authorDhar, Rubyen_US
dc.contributor.authorMahajan, Milinden_US
dc.contributor.authorChoudhury, Alinaen_US
dc.contributor.authorWeissman, Shermanen_US
dc.contributor.authorPace, Betty S.en_US
dc.date.accessioned2014-08-08T17:44:38Z
dc.date.available2014-08-08T17:44:38Z
dc.date.created2013-11-06en_US
dc.date.issued2013-11-06en_US
dc.date.submitted2013-05-31en_US
dc.description.abstractThe upstream Gγ-globin cAMP-response element (G-CRE) plays an important role in regulating Gγ-globin expression through binding of ATF2 and its DNA-binding partners defined in this study. ATF2 knockdown resulted in a significant reduction of γ-globin expression accompanied by decreased ATF2 binding to the G-CRE. By contrast, stable ATF2 expression in K562 cells increased γ-globin transcription which was reduced by ATF2 knockdown. Moreover, a similar effect of ATF2 on γ-globin expression was observed in primary erythroid progenitors. To understand the role of ATF2 in γ-globin expression, chromatographically purified G-CRE/ATF2-interacting proteins were subjected to mass spectrometry analysis; major binding partners included CREB1, cJun, Brg1, and histone deacetylases among others. Immunoprecipitation assays demonstrated interaction of these proteins with ATF2 and in vivo GCRE binding in CD34(+) cells undergoing erythroid differentiation which was correlated with γ-globin expression during development. These results suggest synergism between developmental stage-specific recruitments of the ATF2 protein complex and expression of γ-globin during erythropoiesis. Microarray studies in K562 cells support ATF2 plays diverse roles in hematopoiesis and chromatin remodeling.;en_US
dc.description.sponsorship"This work was supported by grant HL69234 from the National Heart, Lung, and Blood Institute to Dr. Betty Pace. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.en_US
dc.identifier.bibliographicCitationLiu, Li, Subhradip Karmakar, Ruby Dhar, Milind Mahajan, et al. 2013. "Regulation of Gγ-Globin Gene by ATF2 and Its Associated Proteins through the cAMP-Response Element." PLOS One 8(11): 78253-e78253.en_US
dc.identifier.issn1932-6203en_US
dc.identifier.issue11en_US
dc.identifier.startpage78253en_US
dc.identifier.urihttp://hdl.handle.net/10735.1/3856
dc.identifier.volume8en_US
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0078253en_US
dc.rightsCC BY 4.0 (Attribution)en_US
dc.rights©2014 The Authors.en_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/legalcodeen_US
dc.sourcePLOS One
dc.subjectChromatinen_US
dc.subjectDNA--Methylationen_US
dc.subjectDNA-binding proteinsen_US
dc.subjectGene expressionen_US
dc.subjectGenetic regulationen_US
dc.titleRegulation of Gγ-Globin Gene By ATF2 and Its Associated Proteins through the Camp-Response Elementen_US
dc.type.genrearticleen_US

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