Abstract
BackgroundThe neural cell adhesion molecule L1 plays a crucial role in development and plasticity of the nervous system. Neural cells thus require precise control of L1 expression.ResultsWe identified a full binding site for nuclear factor I (NFI) transcription factors in the regulatory region of the mouse L1 gene. Electrophoretic mobility shift assay (EMSA) showed binding of nuclear factor I-A (NFI-A) to this site. Moreover, for a brain-specific isoform of NFI-A (NFI-A bs), we confirmed the interaction in vivo using chromatin immunoprecipitation (ChIP). Reporter gene assays showed that in neuroblastoma cells, overexpression of NFI-A bs repressed L1 expression threefold.ConclusionOur findings suggest that NFI-A, in particular its brain-specific isoform, represses L1 gene expression, and might act as a second silencer of L1 in addition to the neural restrictive silencer factor (NRSF).
Highlights
The neural cell adhesion molecule L1 plays a crucial role in development and plasticity of the nervous system
Identification of a full nuclear factor I (NFI) binding site in the first intron of the mouse L1 gene To ask whether Nuclear factor I-A (NFI-A) binds to the murine L1 gene regulatory region, we analyzed the nucleotide sequence of this region [3,5,6] for NFI binding sites, using the Lasergene (DNASTAR Inc., Madison, WI) software suite
NFI-A binds to the regulatory region of the mouse L1 gene in vitro To assess binding of NFI-A to the full NFI recognition motif in the L1 gene regulatory region in vitro, electrophoretic mobility shift assays (EMSAs) were performed, using both the ubiquitous "standard" isoform of NFI-A (NFI-A st) and a brain-specific isoform (NFI-A bs) [14]
Summary
The neural cell adhesion molecule L1 plays a crucial role in development and plasticity of the nervous system. Targeted ablation of L1 in mice leads to hydrocephalus, corpus callosum hypoplasia, and malformation of the corticospinal tract resembling mutations in the human L1 gene that result in an X-linked recessive neurological disorder called X-linked hydrocephalus, MASA syndrome or spastic paraplegia type I (SPG1) (reviewed by [1]). These observations in mice and man point to a key role of L1 in development of the nervous system. We tested whether NFI-A binds to the murine L1 gene regulatory region and influences L1 gene expression
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