Abstract:In the absence of cut gene activity in Drosophila, external sensory organs are transformed into chordotonal organs. Here we show that the cut locus encodes a large protein containing a homoeodomain and is expressed in nuclei of cells in external sensory organs but not in cells within chordotonal organs.
“…In addition, there is an eight amino acid polyalanine tract encoded by bases 522 to 545. Similar polyalanine runs have been previously observed in several developmentally important genes, including engrailed (Macdonald et al, 19861, euenskipped (Poole et al, 1985), runt (Kania et al, 1990), cut (Blochinger et al, 1988), and ouo (Mevel-Ninio et al, 1991) in Drosophila. This motif may form an alpha helix structure in transcription repression domains (Han and Manley, 1993a,b).…”
We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in sue present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-I homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/cA/,ATTAG/A. 0 1995 Wiley-Liss, Inc.
“…In addition, there is an eight amino acid polyalanine tract encoded by bases 522 to 545. Similar polyalanine runs have been previously observed in several developmentally important genes, including engrailed (Macdonald et al, 19861, euenskipped (Poole et al, 1985), runt (Kania et al, 1990), cut (Blochinger et al, 1988), and ouo (Mevel-Ninio et al, 1991) in Drosophila. This motif may form an alpha helix structure in transcription repression domains (Han and Manley, 1993a,b).…”
We report the characterization of Gsh-1, a novel murine homeobox gene. Northern blot analysis revealed a transcript of approximately 2 kb in sue present at embryonic days 10.5, 11.5, and 12.5 of development. The cDNA sequence encoded a proline rich motif, a polyalanine tract, and a homeodomain with strong homology to those encoded by the clustered Hox genes. The Gsh-1 expression pattern was determined for days E8.5 to E13.5 by whole mount and serial section in situ hybridizations. Gsh-1 transcription was restricted to the central nervous system. Expression is present in the neural tube and hindbrain as two continuous, bilaterally symmetrical stripes within neural epithelial tissue. In the mesencephalon, expression is seen as a band across the most anterior portion. There is also diencephalon expression in the anlagen of the thalamus and the hypothalamus as well as in the optic stalk, optic recess, and the ganglionic eminence. Moreover, through the use of fusion proteins containing the Gsh-I homeodomain, we have determined the consensus DNA binding site of the Gsh-1 homeoprotein to be GCT/cA/,ATTAG/A. 0 1995 Wiley-Liss, Inc.
“…CUT-like homeobox 1 (CUX1) is the mammalian orthologue of the Drosophila melanogaster cut (ct) gene 1 . The human CUX1 gene was identified following purification of the CCAAT-displacement protein (CDP), and has also been called CUT-like 1 (CUTL1) and CDP/CUT 2 .…”
“…The Antennapedia class of homeodomaincontaining proteins, which share homology with the Drosophila antennapedia protein, are clustered within four chromosomal regions in rodents and humans and have been implicated in the regulation of pattern formation during early embryogenesis (Krumlauf, 1994). Homeodomain proteins not found within these four chromosomal clusters, including Gtx, constitute a diverse set of transcription factors, many of which are expressed in a tissueor organ-specific manner (Blochlinger et al, 1988;Ingraham et al, 1988;Staudt et al, 1988;Suh et al, 1994). Although down- stream or target genes have not been identified for many of these orphan homeodomain proteins, several of them have been implicated in organogenesis and cell differentiation (Roberts et al, 1994;Slack, 1995).…”
Section: Homeodomain Proteins Gtx and Developmentmentioning
We have investigated the patterns of postnatal brain expression and DNA binding of Gtx, a homeodomain transcription factor. Gtx mRNA accumulates in parallel with the RNAs encoding the major structural proteins of myelin, myelin basic protein (MBP), and proteolipid protein (PLP) during postnatal brain development; Gtx mRNA decreases in parallel with MBP and PLP mRNAs in the brains of myelin-deficient rats, which have a point mutation in the PLP gene. Gtx mRNA is expressed in differentiated, postmitotic oligodendrocytes but is not found in oligodendrocyte precursors or astrocytes. These data thus demonstrate that Gtx is expressed uniquely in differentiated oligodendrocytes in postnatal rodent brain and that its expression is regulated in parallel with the major myelin protein mRNAs, encoding MBP and PLP, under a variety of physiologically relevant circumstances.Using a Gtx fusion protein produced in bacteria, we have confirmed that Gtx is a sequence-specific DNA-binding protein, which binds DNA sequences containing a core AT-rich homeodomain binding site. Immunoprecipitation of labeled DNA fragments encoding either the MBP or PLP promoter regions with this fusion protein has identified several Gtx-binding fragments, and we have confirmed these data using an electrophoretic mobility shift assay. In this way we have identified four Gtx binding sites within the first 750 bp of the MBP promoter and four Gtx binding sites within the first 1.3 kb of the PLP promoter. In addition, inspection of the PLP promoter sequence demonstrates the presence of six additional Gtx binding sites. These data, taken together, strongly suggest that Gtx is important for the function of differentiated oligodendrocytes and may be involved in the regulation of myelin-specific gene expression.
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