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

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

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Title: Regulation of Gγ-Globin Gene By ATF2 and Its Associated Proteins through the Camp-Response Element
Author(s):
Liu, Li;
Karmakar, Subhradip;
Dhar, Ruby;
Mahajan, Milind;
Choudhury, Alina;
Weissman, Sherman;
Pace, Betty S.
Date Created: 2013-11-06
Item Type: article
Keywords: Show Keywords
Abstract: The 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.;
ISSN: 1932-6203
Source: PLOS One
Link to Related Resource: http://dx.doi.org/10.1371/journal.pone.0078253
Persistent Link: http://hdl.handle.net/10735.1/3856
Bibliographic Citation: Liu, 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.
Terms of Use: CC BY 4.0 (Attribution)
©2014 The Authors.
Sponsors: "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.

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CC BY 4.0 (Attribution) Except where otherwise noted, this item's license is described as CC BY 4.0 (Attribution)