Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers

Seongjin Seo; Jong-Won Lim; Dhananjay Yellajoshyula; Li-Wei Chang; Kristen L Kroll

doi:10.1038/sj.emboj.7601923

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Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers

Journal article

Open access

Peer reviewed

Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers

Seongjin Seo, Jong-Won Lim, Dhananjay Yellajoshyula, Li-Wei Chang and Kristen L Kroll

The EMBO journal, Vol.26(24), pp.5093-5108

12/12/2007

DOI: 10.1038/sj.emboj.7601923

PMCID: PMC2140110

PMID: 18007592

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https://doi.org/10.1038/sj.emboj.7601923View

Published (Version of record) Open Access

Abstract

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.

Embryo, Nonmammalian - anatomy & histology

Oligonucleotide Array Sequence Analysis

Xenopus Proteins - genetics

Gene Expression Profiling

Helix-Loop-Helix Motifs

Recombinant Fusion Proteins - metabolism

Ectoderm - metabolism

In Situ Hybridization

Basic Helix-Loop-Helix Transcription Factors - metabolism

Transcription, Genetic

Embryo, Nonmammalian - physiology

Promoter Regions, Genetic

Basic Helix-Loop-Helix Transcription Factors - genetics

Xenopus laevis - embryology

Animals, Genetically Modified

Gene Expression Regulation

RNA Caps

Nerve Tissue Proteins - genetics

Nerve Tissue Proteins - metabolism

Animals

Enhancer Elements, Genetic

Xenopus laevis - metabolism

Recombinant Fusion Proteins - genetics

Xenopus Proteins - metabolism

Mice

Details

Title: Subtitle: Neurogenin and NeuroD direct transcriptional targets and their regulatory enhancers
Creators: Seongjin Seo - Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, MO 63110, USA
Jong-Won Lim
Dhananjay Yellajoshyula
Li-Wei Chang
Kristen L Kroll
Resource Type: Journal article
Publication Details: The EMBO journal, Vol.26(24), pp.5093-5108
Publisher: England
DOI: 10.1038/sj.emboj.7601923
PMID: 18007592
PMCID: PMC2140110
ISSN: 1460-2075
eISSN: 1460-2075
Grant note: GM66815-01 / NIGMS NIH HHS HG00249 / NHGRI NIH HHS R01 GM066815 / NIGMS NIH HHS U01 GM063340 / NIGMS NIH HHS R01 HG000249 / NHGRI NIH HHS GM63340 / NIGMS NIH HHS
Language: English
Date published: 12/12/2007
Academic Unit: Ophthalmology and Visual Sciences
Record Identifier: 9983980008302771

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