RESUMO
Inherited defects of skull ossification often manifest as symmetric parietal foramina (PFM; MIM 168500). We previously identified mutations of MSX2 in non-syndromic PFM and demonstrated genetic heterogeneity. Deletions of 11p11-p12 (proximal 11p deletion syndrome, P11pDS; MIM 601224) are characterized by multiple exostoses, attributable to haploinsufficiency of EXT2 and PFM. Here we identify ALX4, which encodes a paired-related homeodomain transcription factor, as the PFM disease gene in P11pDS.
Assuntos
Anormalidades Craniofaciais/genética , Proteínas de Ligação a DNA , Genes Homeobox/genética , Mutação/genética , Osteogênese/genética , Proteínas/genética , Crânio/anormalidades , Animais , Sequência de Bases , Análise Mutacional de DNA , Éxons/genética , Proteínas de Homeodomínio/genética , Humanos , Camundongos , Dados de Sequência Molecular , Fenótipo , Mapeamento Físico do Cromossomo , Crânio/embriologia , Fatores de Transcrição/genéticaRESUMO
We have identified a novel zinc finger gene, ZNF232, mapped to human chromosome 17p12. The coding region of the gene is organized in three exons corresponding to a 417 amino acid long polypeptide containing a SCAN/LeR domain and five C(2)H(2)-type zinc fingers. ZNF232 is possibly a nuclear protein, as suggested by expression analysis of GFP/ZNF232 chimeric constructs. ZNF232 transcripts were detected in a wide collection of adult human tissues. The gene is possibly subjected to tissue-specific post-transcriptional regulation by means of alternative splicing.
Assuntos
Genes , Proteínas Nucleares/genética , Dedos de Zinco , Sequência de Aminoácidos , Sequência de Bases , Mapeamento Cromossômico , DNA Complementar/química , Éxons , Biblioteca Gênica , Proteínas de Fluorescência Verde , Humanos , Hibridização In Situ , Íntrons , Proteínas Luminescentes , Masculino , Dados de Sequência Molecular , Células Tumorais CultivadasAssuntos
Proteína da Polipose Adenomatosa do Colo/genética , Polipose Adenomatosa do Colo/genética , Nucleotídeos/genética , Mutação Puntual , Processamento Alternativo , Sequência de Bases , Códon , Neoplasias Colorretais/genética , Análise Mutacional de DNA , Saúde da Família , Humanos , Dados de Sequência MolecularRESUMO
Fre1p and Fre2p are ferric reductases which account for the total plasma membrane associated activity, a prerequisite for iron uptake, in Saccharomyces cerevisiae. The two genes are transcriptionally induced by iron depletion. In this communication, we provide evidence that Fre2p has also cupric reductase activity, as has been previously shown for Fre1p (Hassett, R., and Kosman, D.J. (1995) J. Biol. Chem. 270, 128-134). Both Fre1p and Fre2p enzymes are functionally significant for copper uptake, as monitored by the accumulation of the copper-regulated CUP1 and CTR1 mRNAs in fre1Delta, fre2Delta, and fre1Deltafre2Delta mutant strains. However, only Fre1p activity is induced by copper depletion, even in the presence of iron. This differential copper-dependent regulation of Fre1p and Fre2p is exerted at the transcriptional level of the two genes. We have shown that Mac1p, known to affect the basal levels of FRE1 gene expression (Jungmann, J., Reins, H.-A., Lee, J., Romeo, A., Hassett, R., Kosman, D., and Jentsch, S. (1993) EMBO J. 12, 5051-5056), accounts for both the copper-dependent induction of FRE1 and down-regulation of FRE2 gene. Finally, Mac1p transcriptional activation function is itself modulated by the availability of copper.