An astrocyte-specific enhacer of the aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements

Yoichiro Abe, Hiroko Ikeshima-Kataoka, Wakami Goda, Takako Niikura, Masato Yasui

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)899-912
Number of pages14
JournalJournal of Neurochemistry
Volume120
Issue number6
DOIs
Publication statusPublished - 2012 Mar
Externally publishedYes

Keywords

  • Aquaporin-4
  • Astrocytes
  • Enhancer
  • POU
  • Transcription

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Fingerprint Dive into the research topics of 'An astrocyte-specific enhacer of the aquaporin-4 gene functions through a consensus sequence of POU transcription factors in concert with multiple upstream elements'. Together they form a unique fingerprint.

  • Cite this