Liu, LiKarmakar, SubhradipDhar, RubyMahajan, MilindChoudhury, AlinaWeissman, ShermanPace, Betty S.2014-08-082014-08-082013-11-062013-11-062013-05-311932-6203http://hdl.handle.net/10735.1/3856The 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.;CC BY 4.0 (Attribution)©2014 The Authors.http://creativecommons.org/licenses/by/4.0/legalcodeChromatinDNA--MethylationDNA-binding proteinsGene expressionGenetic regulationarticleLiu, 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-e78253.81178253