TITLE

The FU gene and its possible protein isoforms

AUTHOR(S)
Østerlund, Torben; Everman, David B.; Betz, Regina C.; Mosca, Monica; Nöthen, Markus M.; Schwartz, Charles E.; Zaphiropoulos, Peter G.; Toftgård, Rune
PUB. DATE
January 2004
SOURCE
BMC Genomics;2004, Vol. 5, p1
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: FU is the human homologue of the Drosophila gene fused whose product fused is a positive regulator of the transcription factor Cubitus interruptus (Ci). Thus, FU may act as a regulator of the human counterparts of Ci, the GLI transcription factors. Since Ci and GLI are targets of Hedgehog signaling in development and morphogenesis, it is expected that FU plays an important role in Sonic, Desert and/or Indian Hedgehog induced cellular signaling. Results: The FU gene was identified on chromosome 2q35 at 217.56 Mb and its exon-intron organization determined. The human developmental disorder Syndactyly type 1 (SD1) maps to this region on chromosome 2 and the FU coding region was sequenced using genomic DNA from an affected individual in a linked family. While no FU mutations were found, three single nucleotide polymorphisms were identified. The expression pattern of FU was thoroughly investigated and all examined tissues express FU. It is also clear that different tissues express transcripts of different sizes and some tissues express more than one transcript. By means of nested PCR of specific regions in RT/PCR generated cDNA, it was possible to verify two alternative splicing events. This also suggests the existence of at least two additional protein isoforms besides the FU protein that has previously been described. This long FU and a much shorter isoform were compared for the ability to regulate GLI1 and GLI2. None of the FU isoforms showed any effects on GLI1 induced transcription but the long form can enhance GLI2 activity. Apparently FU did not have any effect on SUFU induced inhibition of GLI. Conclusions: The FU gene and its genomic structure was identified. FU is a candidate gene for SD1, but we have not identified a pathogenic mutation in the FU coding region in a family with SD1. The sequence information and expression analyses show that transcripts of different sizes are expressed and subjected to alternative splicing. Thus, mRNAs may contain different 5'UTRs and encode different protein isoforms. Furthermore, FU is able to enhance the activity of GLI2 but not of GLI1, implicating FU in some aspects of Hedgehog signaling.
ACCESSION #
28859339

 

Related Articles

  • Structure and function of a transcriptional network activated by the MAPK Hog1. Capaldi, Andrew P; Kaplan, Tommy; Liu, Ying; Habib, Naomi; Regev, Aviv; Friedman, Nir; O'Shea, Erin K // Nature Genetics;Nov2008, Vol. 40 Issue 11, p1300 

    Cells regulate gene expression using a complex network of signaling pathways, transcription factors and promoters. To gain insight into the structure and function of these networks, we analyzed gene expression in single- and multiple-mutant strains to build a quantitative model of the Hog1...

  • The regulation of CD5 expression in murine T cells. Tung, James W.; Kunnavatana, Shaun S.; Herzenberg, Leonard A.; Herzenberg, Leonore A. // BMC Molecular Biology;2001, Vol. 2, p5 

    Background: CD5 is a pan-T cell surface marker that is also present on a subset of B cells, B-1a cells.Functional and developmental subsets of T cells express characteristic CD5 levels that vary over roughly a 30-fold range. Previous investigators have cloned a 1.7 Kb fragment containing the CD5...

  • Onecut transcription factor OC2 is a direct target of T-bet in type-1 T-helper cells. Furuno, K.; Ikeda, K.; Hamano, S.; Fukuyama, K.; Sonoda, M.; Hara, T.; Sasazuki, T.; Yamamoto, K. // Genes & Immunity;Jun2008, Vol. 9 Issue 4, p302 

    T-box transcription factor, T-bet, has a central role in the differentiation of T-helper (Th) progenitor cells to Th1 or Th2 effector cells, partly by regulating the expression of genes such as interferon-γ (IFN-γ). However, the direct target genes, especially those mediating the...

  • Assessing quality and completeness of human transcriptional regulatory pathways on a genome-wide scale. Shmelkov, Evgeny; Zuojian Tang; Aifantis, Iannis; Statnikov, Alexander // Biology Direct;2011, Vol. 6 Issue 1, p15 

    Background: Pathway databases are becoming increasingly important and almost omnipresent in most types of biological and translational research. However, little is known about the quality and completeness of pathways stored in these databases. The present study conducts a comprehensive...

  • Role of regucalcin in cell nuclear regulation: involvement as a transcription factor. Yamaguchi, Masayoshi // Cell & Tissue Research;Nov2013, Vol. 354 Issue 2, p331 

    Regucalcin (RGN/SMP30) was discovered in 1978 as a calcium (Ca)-binding protein that contains no EF-hand motif of the Ca-binding domain. The name of regucalcin was proposed for this Ca-binding protein, which can regulate various Ca-dependent enzyme activations in liver cells. The regucalcin gene...

  • Chromatin decouples promoter threshold from dynamic range. Lam, Felix H.; Steger, David J.; O'Shea, Erin K. // Nature;5/8/2008, Vol. 453 Issue 7192, p246 

    Chromatin influences gene expression by restricting access of DNA binding proteins to their cognate sites in the genome. Large-scale characterization of nucleosome positioning in Saccharomyces cerevisiae has revealed a stereotyped promoter organization in which a nucleosome-free region (NFR) is...

  • Purine-mediated signalling triggers eye development. Massé, Karine; Bhamra, Surinder; Eason, Robert; Dale, Nicholas; Jones, Elizabeth A. // Nature;10/25/2007, Vol. 449 Issue 7165, p1058 

    A conserved network of eye field transcription factors (EFTFs) underlies the development of the eye in vertebrates and invertebrates. To direct eye development, Pax6, a key gene in this network, interacts with genes encoding other EFTFs such as Rx1 and Six3 (refs 4–6). However, the...

  • A self-organizing system of repressor gradients establishes segmental complexity in Drosophila. Clyde, Dorothy E.; Corado, Maria S.G.; Xuelin Wu; Paré, Adam; Papatsenko, Dmitri; Small, Stephen // Nature;12/18/2003, Vol. 426 Issue 6968, p849 

    Gradients of regulatory factors are essential for establishing precise patterns of gene expression during development; however, it is not clear how patterning information in multiple gradients is integrated to generate complex body plans. Here we show that opposing gradients of two Drosophila...

  • Co-regulated transcriptional networks contribute to natural genetic variation in Drosophila sleep. Harbison, Susan T.; Carbone, Mary Anna; Ayroles, Julien F.; Stone, Eric A.; Lyman, Richard F.; Mackay, Trudy F. C. // Nature Genetics;Mar2009, Vol. 41 Issue 3, p371 

    Sleep disorders are common in humans, and sleep loss increases the risk of obesity and diabetes. Studies in Drosophila have revealed molecular pathways and neural tissues regulating sleep; however, genes that maintain genetic variation for sleep in natural populations are unknown. Here, we...

Share

Read the Article

Courtesy of THE LIBRARY OF VIRGINIA

Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics