Disease relevance of Gtf2ird1

• Integration of a c-myc transgene results in disruption of the mouse Gtf2ird1 gene, the homologue of the human GTF2IRD1 gene hemizygously deleted in Williams-Beuren syndrome [1].

High impact information on Gtf2ird1

• MusTRD1/BEN has five or six direct repeats, each containing helix--loop--helix motifs, and, thus, belongs to the TFII-I family of transcription factors [2].
• We have used a yeast one-hybrid screen in a search for transcription factors that bind to EE motifs and have isolated a novel murine DNA-binding protein, termed BEN (binding factor for early enhancer) [3].
• 5. Several BEN-encoded polypeptides of different sizes ranging from 165 to 40 kDa were identified by Western blot analysis using BEN-specific polyclonal Abs [3].
• The BEN gene produces several major transcripts (3.6, 4.4, and 5.9 kb) present in most adult tissues and shows discrete spatial and temporal domains of expression in areas of epithelial-mesenchymal interaction during mouse embryogenesis from E9.5 to E12 [3].
• Overexpression of BEN in P19 cells represses the TGFbeta-mediated transcriptional activation of Gsc [4].

Biological context of Gtf2ird1

• Loss of the 5' end of the Gtf2ird1 gene resulted in greatly reduced expression of Gtf2ird1 mRNA in mice homozygous for the transgene [1].
• The helix-loop-helix repeats of Gtf2ird1 and Gtf2i are encoded separately on adjacent exons and were generated by independent genomic rearrangements [5].
• Genomic organization of the genes Gtf2ird1, Gtf2i, and Ncf1 at the mouse chromosome 5 region syntenic to the human chromosome 7q11.23 Williams syndrome critical region [5].
• Regulation of alternative splicing of Gtf2ird1 and its impact on slow muscle promoter activity [6].
• We delineated the consensus sequence G(TC)G(A)GATTA(G)BG(A) for repeat 4 and showed that binding sites for GTF3 in enhancers for Troponin I and homeobox c8 (HOXc8) are in very good agreement with this motif [7].

Anatomical context of Gtf2ird1

• Using RT-PCR, we detected Gtf2i and Gtf2ird1 mRNA transcripts in unfertilized oocytes, which indicates the maternal expression of these genes [8].
• BEN, at this stage, is expressed only in the cytoplasm of trophoblast cells, but not in the ICM [Gene Expr. Patterns, 2003; 3, 577-587] [8].
• Dominant-negative and RNAi-mediated knockdown experiments indicate that BEN can both positively and negatively regulate IgH promoter activity, depending on the cell line [9].

Other interactions of Gtf2ird1

• Comparison of the genomic DNA structure in wildtype and transgenic mice revealed that the transgene integration had induced an approximately 40-kb deletion, starting downstream of the Cyln2 gene and including the first exon of the Gtf2ird1 gene [1].
• CONCLUSIONS: These studies indicate that a genomic rearrangement affecting Nid or Estm9 does not underlie bg [10].

References