Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation Journal Article


Authors: Ebert, P. J.; Timmer, J. R.; Nakada, Y.; Helms, A. W.; Parab, P. B.; Liu, Y.; Hunsaker, T. L.; Johnson, J. E.
Article Title: Zic1 represses Math1 expression via interactions with the Math1 enhancer and modulation of Math1 autoregulation
Abstract: Math1 is a basic helix-loop-helix transcription factor expressed in progenitor cells that give rise to dorsal commissural interneurons in the spinal cord, granule cells of the cerebellum, and sensory cells in the inner ear and skin. Transcriptional regulation of this gene is tightly controlled both temporally and spatially during nervous system development. The signals that mediate this regulation are likely integrated at the Math1 enhancer, which is highly conserved among vertebrate species. We have identified the zinc-finger transcription factor Zic1 as a regulator of Math1 expression. Zic1 binds a novel conserved site within the Math1 enhancer, and represses both the expression of endogenous Cath1 (chicken homolog of Math1) and the activity of a Math1 enhancer driven lacZ reporter when expressed in chick neural tubes. Repression by Zic1 blocks the autoregulatory activity of Math1 itself. Although previous reports have shown that Zic1 and Math1 are both induced by BMP signaling, these genes appear to have opposing functions, as Math1 acts to promote neuronal differentiation in the chick neural tube and excess Zic1 appears to block differentiation. Zic1-mediated repression of Cath1 transcription may modulate the temporal switch between the progenitor state and differentiating dorsal cell types during neural tube development.
Keywords: signal transduction; controlled study; protein expression; unclassified drug; review; nonhuman; mouse; animals; animal tissue; bone morphogenetic protein; embryo; protein protein interaction; basic helix-loop-helix transcription factors; protein binding; transcription factor; gene function; cell type; animalia; transcription factors; stem cell; vertebrata; gene expression regulation, developmental; transcription regulation; conserved sequence; nucleotide sequence; gene repression; beta galactosidase; reporter gene; base sequence; binding sites; zinc finger protein; nerve cell differentiation; transgenes; neural tube; transcriptional regulation; regulator protein; autoregulation; chick embryo; bone morphogenetic proteins; enhancer region; neuronal differentiation; animals, genetically modified; chicken; helix loop helix protein; enhancer elements (genetics); helix-loop-helix motifs; priority journal; gallus gallus; bhlh trascription factors; chick electroporation; dorsal spinal cord development; mash1/cash1; math1/cath1; ngn1; ngn2; transcription repressors; protein cath1; protein math1; protein zic1
Journal Title: Development
Volume: 130
Issue: 9
ISSN: 0950-1991
Publisher: Company of Biologists  
Date Published: 2003-05-01
Start Page: 1949
End Page: 1959
Language: English
DOI: 10.1242/dev.00419
PUBMED: 12642498
PROVIDER: scopus
DOI/URL:
Notes: Export Date: 25 September 2014 -- Molecular Sequence Numbers: GENBANK: AF218258, AF467292; -- Source: Scopus
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  1. John Timmer
    8 Timmer