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EMBO J December 12, 2007; 26 (24): 5093-108.

Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers.

Seo S , Lim JW , Yellajoshyula D , Chang LW , Kroll KL .

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.

PubMed ID: 18007592
PMC ID: PMC2140110
Article link: EMBO J
Grant support: [+]
Genes referenced: amotl2 cbfa2t2 cnn1 dbn1 dll1 ebf2 ebf3 elavl3 flvcr2 fzd7 gng13 lims1 neurod1 neurod4 neurog1 nhlh1 pdk4 pou3f1 ranbp1 slc7a7 znf238.2
Morpholinos: neurog2 MO2 neurog2 MO3

Article Images: [+] show captions
References [+] :
Bellefroid, X-MyT1, a Xenopus C2HC-type zinc finger protein with a regulatory function in neuronal differentiation. 1997, Pubmed, Xenbase

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