Regulation of Gγ-Globin Gene by ATF2 and Its Associated Proteins through the cAMP-Response Element
نویسندگان
چکیده
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.
منابع مشابه
Characterization and functional analysis of cAMP response element modulator protein and activating transcription factor 2 (ATF2) isoforms in the human myometrium during pregnancy and labor: identification of a novel ATF2 species with potent transactivation properties.
There is now extensive evidence to indicate that components of the cAMP signaling pathway are up-regulated in the human myometrium during pregnancy so as to potentiate the maintenance of uterine quiescence until term. In many tissue and cell types, increased signaling of the cAMP pathway results in profound changes in gene expression that are catalyzed via stimulation of PKA and activation of c...
متن کاملCompetitive binding of CREB and ATF2 to cAMP/ATF responsive element regulates eNOS gene expression in endothelial cells.
OBJECTIVE Expression of endothelial nitric oxide synthase (eNOS) is a critical determinant for vascular homeostasis. We examined the effects of Beraprost sodium (BPS), a stable analogue of prostacyclin, on the eNOS gene expression in the presence of inflammatory cytokine interleukin (IL)-1beta in cultured endothelial cells. METHOD AND RESULTS Exposure of human and bovine endothelial cells to ...
متن کاملcAMP-response elements in Aplysia creb1, creb2, and Ap-uch promoters: implications for feedback loops modulating long term memory.
The Aplysia genes encoding for cAMP-response element-binding protein 1 (CREB1), CREB2, and ubiquitin C-terminal hydrolase (Ap-uch) have been implicated in the formation of long term memory. However, nothing is known about the promoter regions of these genes or the transcription factors that regulate them. We cloned the promoter regions of creb1, creb2, and Ap-uch and identified a canonical cAMP...
متن کاملExpression of the cyclic AMP-dependent transcription factors, CREB, CREM and ATF2, in the human myometrium during pregnancy and labour.
Elevated concentrations of cyclic AMP (cAMP) in the human myometrium may promote uterine quiescence during pregnancy by protein kinase A (PKA)-mediated phosphorylation and subsequent inactivation of myosin light-chain kinase, as well as by the phosphorylation and activation of cAMP-dependent transcription factors. In this context, we show that the altered expression of cAMP response-element bin...
متن کاملStress-induced Fas ligand expression in T cells is mediated through a MEK kinase 1-regulated response element in the Fas ligand promoter.
T lymphocytes undergo apoptosis in response to a variety of stimuli, including exposure to UV radiation and gamma-irradiation. While the mechanism by which stress stimuli induce apoptosis is not well understood, we have previously shown that the induction of Fas ligand (FasL) gene expression by environmental stress stimuli is dependent on c-Jun N-terminal kinase (JNK) activation. Using inducibl...
متن کامل