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

Li Liu, Subhradip Karmakar, Ruby Dhar, Milind Mahajan, Alina Choudhury, Sherman Weissman, Betty Sue Pace

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbere78253
JournalPloS one
Volume8
Issue number11
DOIs
StatePublished - Nov 6 2013

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Globins
response elements
Response Elements
Genes
erythropoiesis
Proteins
hematopoiesis
genes
proteins
synergism
cells
histones
chromatin
transcription (genetics)
developmental stages
mass spectrometry
K562 Cells
DNA
assays
Erythroid Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Regulation of Gγ-globin gene by ATF2 and its associated proteins through the cAMP-response element. / Liu, Li; Karmakar, Subhradip; Dhar, Ruby; Mahajan, Milind; Choudhury, Alina; Weissman, Sherman; Pace, Betty Sue.

In: PloS one, Vol. 8, No. 11, e78253, 06.11.2013.

Research output: Contribution to journalArticle

Liu, Li ; Karmakar, Subhradip ; Dhar, Ruby ; Mahajan, Milind ; Choudhury, Alina ; Weissman, Sherman ; Pace, Betty Sue. / Regulation of Gγ-globin gene by ATF2 and its associated proteins through the cAMP-response element. In: PloS one. 2013 ; Vol. 8, No. 11.
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