title: Transcriptional regulation of mouse neuroglobin gene by cyclic AMP responsive element binding protein (CREB) in N2a cells.
abstract: Neuroglobin (Ngb) has been demonstrated to be a novel neuroprotective protein that protects against hypoxia/ischemia and oxidative stress-induced injury in the nervous system. However, the regulation mechanisms of Ngb gene expression under both normal resting and stress conditions have not been fully elucidated. The cyclic AMP response element binding protein (CREB) is a key transcription factor that regulates a variety of pro-survival genes, but its role in regulating the neuroprotective gene Ngb has not been studied. In this study we investigated the transcriptional regulation of mouse Ngb gene by CREB in mouse neuroblastoma cell line N2a. Our results showed that CREB knockdown decreased Ngb gene expression, and overexpression of the wild-type CREB, but not the mutant CREB, significantly increased Ngb gene expression in N2a cells. Moreover, a cAMP response element (CRE) site located at -854 in the promoter region of mouse Ngb gene was found to be responsible for both basal and CREB-induced Ngb promoter activity. Using chromatin immunopreciptation (ChIP) assays, we found that CREB could bind to the Ngb promoter region spanning from -1016 to -793 that harbors the CRE site. Taken together, our results suggested that transcription factor CREB participates in the transcriptional regulation of mouse Ngb gene.
authors.affiliation: Neuroprotection Research Laboratory, Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.
authors.forename: Ning
authors.initials: N
authors.lastname: Liu
authors.forename: Zhanyang
authors.initials: Z
authors.lastname: Yu
authors.forename: Yadan
authors.initials: Y
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Shuanglin
authors.initials: S
authors.lastname: Xiang
authors.forename: Xiaoying
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D017362:Cyclic AMP Response Element-Binding Protein / Q000502:physiology*; D005786:Gene Expression Regulation; D005914:Globins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D014158:Transcription, Genetic
chemical_list: C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins