Regulation of G?-globin gene by ATF2 and its associated proteins through the cAMP-response element.

ABSTRACT: The upstream G?-globin cAMP-response element (G-CRE) plays an important role in regulating G?-globin expression through binding of ATF2 and its DNA-binding partners defined in this study. ATF2 knockdown resulted in a significant reduction of ?-globin expression accompanied by decreased ATF2 binding to the G-CRE. By contrast, stable ATF2 expression in K562 cells increased ?-globin transcription which was reduced by ATF2 knockdown. Moreover, a similar effect of ATF2 on ?-globin expression was observed in primary erythroid progenitors. To understand the role of ATF2 in ?-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 ?-globin expression during development. These results suggest synergism between developmental stage-specific recruitments of the ATF2 protein complex and expression of ?-globin during erythropoiesis. Microarray studies in K562 cells support ATF2 plays diverse roles in hematopoiesis and chromatin remodeling.

SUBMITTER: Liu L 

PROVIDER: S-EPMC3819381 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature