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An astrocyte‐specific enhancer of the aquaporin‐4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements
Author(s) -
Abe Yoichiro,
IkeshimaKataoka Hiroko,
Goda Wakami,
Niikura Takako,
Yasui Masato
Publication year - 2012
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2012.07652.x
Subject(s) - enhancer , pou domain , astrocyte , promoter , biology , gene isoform , exon , enhancer rnas , transcription (linguistics) , transcription factor , microbiology and biotechnology , gene , ccaat enhancer binding proteins , regulatory sequence , aquaporin 4 , gene expression , genetics , dna binding protein , biochemistry , neuroscience , linguistics , philosophy , homeobox , central nervous system
J. Neurochem. (2012) 120 , 899–912. Abstract Aquaporin‐4, a predominant water channel in the brain, is specifically expressed in astrocyte endfeet and plays a central role in water homeostasis, neuronal activity, and cell migration in the brain. It has two dominant isoforms called M1 and M23, whose mRNA is driven by distinct promoters located upstream of exons 0 and 1 of the aquaporin‐4 gene, respectively. To identify cis ‐acting elements responsible for the astrocyte‐specific transcription of M1 mRNA, the promoter activity of the 5′‐flanking region upstream of exon 0 in primary cultured mouse astrocytes was examined by luciferase assay, and sequences, where nuclear factors bind, were identified by electrophoretic mobility shift assay. An astrocyte‐specific activity enhancing transcription from the M1 promoter was observed within ∼2 kb from the transcriptional start sites of M1 mRNA. At least five elements clustered within the 286‐bp region were found to function as a novel astrocyte‐specific enhancer. Among the five elements, a consensus sequence of Pit‐1/Oct/Unc‐86 (POU) transcription factors was indispensable to the astrocyte‐specific enhancer since disruption of the POU motif completely abolished the enhancer activity in astrocytes. However, the POU motif alone had little activity, indicating the requirement for cooperation with other upstream elements to exert full enhancer activity.