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| Subject Categories: Chromatin & Transcription | Development |
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| The EMBO Journal
(2007) 26, 5093–5108, doi:10.1038/sj.emboj.7601923 Published online 15 November 2007 |
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| Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers |
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| Seongjin Seo1, 3, Jong-Won Lim1, 3, Dhananjay Yellajoshyula1, Li-Wei Chang2 and Kristen L Kroll1 |
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1 Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO, USA 2 Department of Biomedical Engineering, Washington University, St Louis, MO, USA To whom correspondence should be addressed Kristen L Kroll, Department of Molecular Biology and Pharmacology, Washington University School of Medicine, Campus Box 8103, 660 S Euclid Avenue, St Louis, MO 63110, USA. Tel.: +1 314 362 7045; Fax: +1 314 362 7058; E-mail: kkroll@wustl.edu 3 These authors contributed equally to this work Received 14 September 2007; Accepted 19 October 2007; Published online 15 November 2007. |
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| Abstract |
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| Proneural basic helix–loop–helix proteins are key regulators of neurogenesis but their 'proneural' function is not well understood, partly because primary targets have not been systematically defined. Here, we identified direct transcriptional targets of the bHLH proteins Neurogenin and NeuroD and found that primary roles of these transcription factors are to induce regulators of transcription, signal transduction, and cytoskeletal rearrangement for neuronal differentiation and migration. We determined targets induced in both Xenopus and mouse, which represent evolutionarily conserved core mediators of Neurogenin and NeuroD activities. We defined consensus sequences for Neurogenin and NeuroD binding and identified responsive enhancers in seven shared target genes. These enhancers commonly contained clustered, conserved consensus-binding sites and drove neural-restricted transgene expression in Xenopus embryos. We then used this enhancer signature in a genome-wide computational approach to predict additional Neurogenin/NeuroD target genes involved in neurogenesis. Taken together, these data demonstrate that Neurogenin and NeuroD preferentially recognize neurogenesis-related targets through an enhancer signature of clustered consensus-binding sites and regulate neurogenesis by activating a core set of transcription factors, which build a robust network controlling neurogenesis. |
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| Keywords: E-box, enhancer, NeuroD, neurogenesis, Neurogenin |
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Top of page MORE ARTICLES LIKE THISThese links to content published by NPG are automatically generated RESEARCHDisruption of positive selection of thymocytes causes autoimmunity Nature Medicine Article (01 Mar 2000) Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers The EMBO Journal Article XPak3 promotes cell cycle withdrawal during primary neurogenesis in Xenopus laevis The EMBO Journal Article (01 Dec 2002) The EMBO Journal Article (16 Oct 2000) |
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