Role of upstream stimulating factors in the transcriptional regulation of the neuron-specific K-Cl cotransporter KCC2

Marika Markkanen, Pavel Uvarov, Matti S Airaksinen

    Research output: Contribution to journalArticleScientificpeer-review


    The neuron-specific K-Cl cotransporter (KCC2) maintains a low intracellular Cl- concentration in neurons and is necessary for fast hyperpolarizing responses to GABA and glycine. The mammalian KCC2 gene (alias Slc12a5) generates two neuron-specific isoforms by using alternative promoters and first exons. Expression of the major isoform, KCC2b, is strongly upregulated during neuronal maturation, and is modulated by neuronal activity, trauma, and neurotrophic factors. in the present study, we have focused on the regulatory influence of the upstream stimulating factors USF1 and USF2 via an E-box control element in the KCC2b promoter (E-box(KCC2b)). Electrophoretic mobility shift assay in cell lines and chromatin immunoprecipitation in neurons demonstrated binding of endogenous USF1 and USF2 to the E-box(KCC2b) element. Mutation of the E-box(KCC2b) site resulted in reduced KCC2b promoter activity in cell lines and cortical neurons. Overexpression of a dominant-negative form of USF confirmed the involvement of endogenous USF proteins in the regulation of the KCC2b gene. The results suggest that binding of USF proteins to the E-box(KCC2b) may contribute to the upregulation of KCC2b gene expression in developing brain. (C) 2008 Elsevier B.V. All rights reserved.
    Original languageEnglish
    JournalBrain Research
    Pages (from-to)8-15
    Number of pages8
    Publication statusPublished - 2008
    MoE publication typeA1 Journal article-refereed

    Fields of Science

    • 311 Basic medicine
    • 118 Biological sciences
    • 515 Psychology

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