Neurog3 11925

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Gene ID: 11925
Gene symbol: neurog3
Gene Description: neurogenin 3
Aliases: Atoh5; Math4B; MGC129292; MGC129293; ngn3
Human Ortholog Gene ID: [50674]
Reviewer Judgement: TF Gene
Functional Classification: DNA-Binding: non-sequence-specific;

DNA-Binding: sequence-specific

DBD Protein Group Classification: Zipper-Type Group
DBD Protein Group/Family Classification: Zipper-Type Group / Helix-Loop-Helix Family
Homolog Cluster(s): 11921; 15206

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[14576336] DNA Binding Human; Rat; Mouse Medium NEUROG3 Promoter Activity Is Dependent upon an E Box Located at -149 bp. The three cell lines shown were transfected with reporter plasmids containing the firefly luciferase gene under the control of the either the wild-type -207-bp NEUROG3 promoter, or the -207-bp NEUROG3 promoter containing a 2-bp mutation in the E box (-207-bp ME).

EMSA were used to test the ability of E47, Neurogenin3, and neuroD1 to bind to labeled, double-stranded oligonucleotides containing the E box sequences from the rat insulin I and mouse nkx2.2 promoters (A) or the human PAX4 and NEUROG3 promoters (B).

Warren Cheung
[16511571] DNA Binding Mouse Medium Ngn3 is a TF.

Rapid and specific induction of IA1 expression in AdHANgn3-transduced adult human duct cells. Activation of IA1 gene expression in adult human pancreatic duct cells is observed following transduction with either AdHANgn3 and, albeit much weaker, AdNeuroD1, but not with adenoviral Foxa1, Foxa2, Pdx1, Pax4, Pax6, Nkx6.1, Nkx2.2 and GFP.

Chromatin immunoprecipitation with an anti-HA antibody or IgG was performed on chromatin derived from isolated human duct cells infected with either HANgn3 or GFP. The IA1 gene promoter is coimmunoprecipitated in the HANgn3-transduced duct cells using an anti-HA antibody but not by addition of IgG. Similarly, NeuroD1, but not BRCA1 or CTLA-4, are specifically co-precipitated by the anti-HA antibody. IA1,NeuroD1, BRCA1 and CTLA-4 are not precipitated in the negative control cells transduced with AdGFP.

Warren Cheung
[10757813] Co-activation; Transactivation Human; Mouse Weak Ngn3 stably transfected into STC-1 and beta-TC cells up-regulated endogenous BETA2 expression. Co-transfection of ngn3 and E47 vectors in HeLa cells increased expression of BETA2 promoter constructs. Magdalena Swanson
[16511571] DNA Binding; Transactivation Human; Mouse Strong IA1 promoter-driven luciferase activity was increased in 293 cells when the reporter was cotransfected with a Ngn3 expression plasmid, and no IA1-expressing cells were detected in pancreas of Ngn3 knockout mice. Chromatin immunoprecipitation using adult human duct cells transduced with AdHANgn3 showed that Ngn3 binds to the promoter regions of the IA1 and NeuroD1 genes. Magdalena Swanson
[16511571] DNA Binding; Transactivation Human Strong GeneID: 11925

Referring to PMID: 16511571

Neurogenin3 (Ngn3) is a TF, which activates expression of IA1. IA1 expression is rapidly and specifically induced in AdHANgn3-transduced adult human duct cells 17 h following transduction, which is earlier than other proposed direct Ngn3 target genes Pax4, NeuroD1 and Nkx2.2. IA1 gene expression is also activated in adult human pancreatic duct cells following transduction with AdHANgn3 but not adenoviral Foxa1, Foxa2, Pdx1, Pax4, Pax6, Nkx6.1, Nkx2.2 and GFP. Cotransfection of IA1 promoter�reporter constructs and Ngn3 into human 293 cells increases IA1 promoter activity by twofold as compared to the IA1 promoter alone.

Ngn3 interacts with the 5' flanking regions of IA1. The IA1 gene promoter coimmunoprecipitates with HA-Ngn3 in HANgn3-transduced adult human duct cells using an anti-HA antibody. IA1, NeuroD1, BRCA1 and CTLA-4 are not precipitated in the negative control cells transduced with AdGFP.

Stuart Lithwick
[10757813] DNA Binding Mouse Medium Transfection assays show ngn3 induces and up-regulates ectopic BETA2 expression. Experiments are conducted with controls.

The effect of ngn3 on a series of reporter constructs bearing different deletions of the BETA2 promoter is assayed. E1 and E3 E boxes are important for ngn3-E47-mediated activation of the BETA2 promoter. Gel shift analyses show ngn3 binds to E1 and E3 but not E2.

Amy Ticoll
[16511571] Non-specific DNA Human Strong Cotransfection of an IA1 promoter�reporter construct with Ngn3 increases IA1 promoter activity by twofold as compared to the IA1 promoter only. Chromatin immunoprecipitation was performed using adult human duct cells transduced with AdHANgn3. Promoter regions of the IA1 gene but not control gene fragments from BRCA1 or CTLA4 were coimmunoprecipitated by HANgn3. Results show that Ngn3 binds and activates the IA1 promoter. Amy Ticoll
Additional Reviewer Comments:
Reviewer: Amy Ticoll

Promoter regions of the IA1 gene are coimmunoprecipitated by Ngn3. Deletion analysis shows sequence specificity of ngn3 for the BETA2 promoter. Transfection assays show ngn3 increases gene expression.

Reviewer: Magdalena Swanson

Neurog3 is a transcription factor. It shows in vivo DNA binding through chromatin immunoprecipitation from adult human duct cells. It transactivates reporter gene constructs alone, or in the presence of transcription factor E2a (E47), depending on the cell line used. It increases the endogenous transcription of the Neurod1 gene (BETA2) in STC-1 and beta-TC cells.

Reviewer: Stuart Lithwick

GeneID: 11925 Referring to PMID:16511571 Ngn3 is a transcription factor, which binds to the IA1 promoter, and activates IA1 gene expression. Expression of IA1 is induced earlier than other known Ngn3 target genes in human cells transduced with exogenous Ngn3 as demonstrated by RT-PCR. IA1 expression is also activated in human cells following transduction with exogenous Ngn3 as demonstrated by RT-PCR. Actvity of a reporter gene fused to the IA1 promoter increases 2-fold when co-transfected with Ngn3, an experiment, which was performed in triplicate. Ngn3 also interacts with the 5' flanking region of the IA1 and NeuroD1 genes as demonstrated by Co-IP.

Reviewer: Warren Cheung

Neurogenin3 is a TF factor. Extensive tests show that it is responsible for regulation of pancreatic cell lines, and regulate the expression of other TF such as IA3. Activity is dependant on a critical "E box" promoter element.


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Facts about Neurog3 11925RDF feed
Gene description neurogenin 3  +
Gene id 11,925  +
Gene judgment TF Gene  +
Gene symbol neurog3  +, Atoh5  +, Math4B  +, MGC129292  +, MGC129293  +, and ngn3  +
Gene taxonomy DNA-Binding: non-sequence-specific  +, and DNA-Binding: sequence-specific  +
Homolog cluster 11,921  +, and 15,206  +
Protein family 3 Zipper-Type Group/22 Helix-Loop-Helix Family  +
Protein group 3 Zipper-Type Group   +
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