Foxa1 15375

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Gene ID: 15375
Gene symbol: foxa1
Gene Description: forkhead box a1
Aliases: Hnf-3a; Hnf3a; Tcf-3a; Tcf3a
Human Ortholog Gene ID: [3169]
Reviewer Judgement: TF Gene
Functional Classification: DNA-Binding: sequence-specific
DBD Protein Group Classification: Winged Helix-Turn-Helix
DBD Protein Group/Family Classification: Winged Helix-Turn-Helix / Forkhead Domain Family
Homolog Cluster(s): 108655

Evidence:

Pubmed ID Function Species Evidence Strength Reviewer's Comments Reviewer
[2227418] DNA Binding Rat Strong HNF-3 is a site found to be important in the maximal hepatocyte-specific expression of several genes. Authors find that liver nuclear extracts contain three major binding activities for this site, which they call HNF-3A, HNF-3B, and HNF-3C. Purification from rat liver nuclear extracts of HNF-3A and HNF-3C reveals that each activity corresponds to a distinct polypeptide. Peptide sequence derived from the most abundant species, HNF-3A, was used for synthesizing probes with which to isolate a cDNA clone of this protein. The encoded protein contains 466 amino acids (48.7 kD) and has binding properties identical to those of the purified protein. A 160-amino-acid region that does not resemble the binding domain of any known transcription factor is essential for DNA binding. The mRNA for HNF-3A is present in the rat liver but not in brain, kidney, intestine, or spleen, and the basis for this difference is cell-specific regulation of HNF-3A gene transcription. Gwenael Breard
[11864602] DNA Binding Human Strong The transcription factors HNF3 (FoxA) and GATA-4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in embryos. To understand how they access sites in silent chromatin, Authors assembled nucleosome arrays containing albumin enhancer sequences and compacted them with linker histone. HNF3 and GATA-4, but not NF-1, C/EBP, and GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes. The ability of HNF3 to open chromatin is mediated by a high affinity DNA binding site and by the C-terminal domain of the protein, which binds histones H3 and H4. Thus, factors that potentiate transcription in development are inherently capable of initiating chromatin opening events. Gwenael Breard
[15485926] DNA Binding Rat Strong Chromatin immunoprecipitation studies demonstrate Foxa1 binding sites in the murine H19 E1 enhancer. Foxa1 binding to elements in the enhancer was confirmed by gel shift studies performed using extracts from HeLa cells transiently transfected with rat Foxa1. Rob Sladek
[15539431] Transactivation Rat Strong Foxa1 activates a reporter controlled by the rat glucagon gene promoter (�292GluCAT) following transient cotransfection in BHK-21 cells. Rob Sladek
Additional Reviewer Comments:
Reviewer: Gwenael Breard

This transcription factor has both a DNA binding - sequence specific activity and a transcription regulation activity by interacting with Histones. The hepatocyte nuclear factors are transcriptional activators for liver-specific transcripts such as albumin and transthyretin. The HNF3 family, including HNF3A, HNF3B, and HNF3G are members of the forkhead class of DNA-binding proteins. The transcription factors Hnf3a and Gata4 are the earliest known to bind the albumin gene enhancer in liver precursor cells in mouse embryos. To determine how they access sites in silent chromatin, Cirillo et al. (2002) assembled nucleosome arrays containing albumin enhancer sequences and compacted them with linker histone. Hnf3a and Gata4, but not human NF1, mouse Cebp-beta, or yeast GAL4-AH, bound their sites in compacted chromatin and opened the local nucleosomal domain in the absence of ATP-dependent enzymes. The authors showed that the ability of Hnf3a to open chromatin is mediated by a high-affinity DNA-binding site and by the C-terminal domain of the protein, which binds histones H3 and H4. They concluded that factors that potentiate transcription in development are inherently capable of initiating chromatin opening events.

Reviewer: Rob Sladek

Chromatin immunoprecipitation studies demonstrate Foxa1 binding sites in the murine H19 E1 enhancer. Foxa1 binding to elements in the enhancer was confirmed by gel shift studies performed using extracts from HeLa cells transiently transfected with rat Foxa1. Foxa1 activates a reporter controlled by the rat glucagon gene promoter (–292GluCAT) following transient cotransfection in BHK-21 cells.


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Facts about Foxa1 15375RDF feed
Gene description forkhead box a1  +
Gene id 15,375  +
Gene judgment TF Gene  +
Gene symbol foxa1  +, Hnf-3a  +, Hnf3a  +, Tcf-3a  +, and Tcf3a  +
Gene taxonomy DNA-Binding: sequence-specific  +
Homolog cluster 108,655  +
Protein family 1.2 Winged Helix-Turn-Helix/102 Forkhead Domain Family  +
Protein group 1.2 Winged Helix-Turn-Helix   +
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