G Spohr

Publications (6)60.47 Total impact

• Article: Localized XId3 mRNA activation in Xenopus embryos by cytoplasmic polyadenylation.

  A B Afouda, S Reynaud-Deonauth, T Mohun, G Spohr
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  ABSTRACT: In Xenopus development, during meiosis and cleavage, the extent of polyadenylation plays a central role in regulating the expression of transcripts and this is mediated by cis regulatory cytoplasmic polyadenylation elements (CPE) in the 3'-UTRs. We have identified a palindromic CPE in the mRNA of Xenopus Id3 which is conserved in the Id genes from other vertebrates. It promotes cytoplasmic polyadenylation and is negatively regulated by sequences further upstream in the 3'-UTR. This palindromic CPE promotes polyadenylation in both the epithelial and sensorial layers of the dorsal ectoderm in early embryos, but association with the upstream negative element blocks this effect in the epithelial layer. The asymmetric polyadenylation may be important for establishing a prepattern of transcriptional regulators.
  Mechanisms of Development 11/1999; 88(1):15-31. · 2.83 Impact Factor
• Article: MEF-2 function is modified by a novel co-repressor, MITR.

  D B Sparrow, E A Miska, E Langley, S Reynaud-Deonauth, S Kotecha, N Towers, G Spohr, T Kouzarides, T J Mohun
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  ABSTRACT: The MEF-2 proteins are a family of transcriptional activators that have been detected in a wide variety of cell types. In skeletal muscle cells, MEF-2 proteins interact with members of the MyoD family of transcriptional activators to synergistically activate gene expression. Similar interactions with tissue or lineage-specific cofactors may also underlie MEF-2 function in other cell types. In order to screen for such cofactors, we have used a transcriptionally inactive mutant of Xenopus MEF2D in a yeast two-hybrid screen. This approach has identified a novel protein expressed in the early embryo that binds to XMEF2D and XMEF2A. The MEF-2 interacting transcription repressor (MITR) protein binds to the N-terminal MADS/MEF-2 region of the MEF-2 proteins but does not bind to the related Xenopus MADS protein serum response factor. In the early embryo, MITR expression commences at the neurula stage within the mature somites and is subsequently restricted to the myotomal muscle. In functional assays, MITR negatively regulates MEF-2-dependent transcription and we show that this repression is mediated by direct binding of MITR to the histone deacetylase HDAC1. Thus, we propose that MITR acts as a co-repressor, recruiting a specific deacetylase to downregulate MEF-2 activity.
  The EMBO Journal 10/1999; 18(18):5085-98. · 9.20 Impact Factor
• Article: Id gene activity during Xenopus embryogenesis.

  H Zhang, S Reynaud, M Kloc, L D Etkin, G Spohr
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  ABSTRACT: The activity of bHLH transcription factors that are involved in cell determination and differentiation is inhibited by Ids, HLH proteins lacking the basic amino acid sequence element. In order to determine the role of Id during development, we have isolated and characterized the Id genes expressed in Xenopus embryos. Three cDNAs were characterized: XIdIa and XIdIb, which are transcribed from one gene but differentially spliced in the 3' untranslated part, and XIdII which is transcribed from a second copy of the gene. One of the two forms of the differentially spliced mRNAs exhibits, 30 nucleotides upstream from the AATAAA site, a sequence box homologous to the cytoplasmic polyadenylation element (CPE) which is present also in Id2 and Id3 mRNAs from higher vertebrates. This raises the question of whether this CPE-like element may link Id mRNA polyadenylation and translation to the cell cycle metabolism. The Xenopus Id gene is transcribed at low level in oocytes and at high level in embryos, after midblastula transition, in a large number of tissues, including the notochord, neural tube, eye, ear, neural crest cells, presomitic mesoderm, myotomes, tailbud and dorsal fin. In myotomes, expression is high in the areas of proliferating myoblasts and decreases as terminal differentiation proceeds, consistent with a function in cell determination and differentiation and possibly also in cell cycle regulation.
  Mechanisms of Development 05/1995; 50(2-3):119-30. · 2.83 Impact Factor
• Article: Translocation of repetitive RNA sequences with the germ plasm in Xenopus oocytes.

  M Kloc, G Spohr, L D Etkin
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  ABSTRACT: Xlsirts are a family of interspersed repeat RNAs from Xenopus laevis that contain from 3 to 13 repeat units (each 79 to 81 nucleotides long) flanked by unique sequences. They are homologous to the mammalian Xist gene that is involved in X chromosome inactivation. Xlsirt RNA appears first in the mitochondrial cloud (Balbiani body) in stage 2 oocytes and is then translocated as island-like structures to the vegetal cortex at early stage 3 coincident with the localization of the germ plasm. Exogenous Xlsirt RNA injected into oocytes translocates to the location of the endogenous RNA at that particular stage. The Xlsirt RNA repeat sequences are required for translocation and can cause the translocation of heterologous unique RNAs to the vegetal cortex.
  Science 01/1994; 262(5140):1712-4. · 31.20 Impact Factor
• Article: Regulation of Xenopus c-myc promoter activity in oocytes and embryos.

  S P Modak, E Principaud, G Spohr
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  ABSTRACT: We have studied the regulation of transcription of the Xenopus c-myc I gene in oocytes and embryos. Various 5' and internal deletions of a 1310-bp-long c-myc I promoter fragment have been ligated upstream of the chloramphenicol acetyl transferase (CAT) reporter gene and microinjected into oocytes and fertilized eggs. Activity was determined by CAT assay and primer extension. The c-myc promoter drives transcription very efficiently, and a truncated promoter -158/+46 essentially retains full activity. This region contains an overlapping E2F/SP1 site and two tandem Sp1 sites homologous to those found in the c-myc gene of mouse. Internal deletions show that both elements are equally active in oocytes in driving the expression of CAT. A germinal vesicle extract contains a DNA-binding activity specific for an Sp1 consensus sequence but not the E2F site. The data suggest that the high transcription level of the endogenous c-myc gene in Xenopus oocytes is mediated by Sp1 or a related transcription factor. In embryos a different mechanism emerges and the functional role of the Sp1 binding sites appears to be less important.
  Oncogene 04/1993; 8(3):645-54. · 6.37 Impact Factor
• Source

  Available from: nih.gov

  Article: Xenopus laevis c-myc I and II genes: molecular structure and developmental expression.

  E Principaud, G Spohr
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  ABSTRACT: The structure of the two Xenopus laevis c-myc I and c-myc II genes has been investigated by isolating and sequencing genomic and cDNAs clones. In oocytes, c-myc I mRNAs represent 80-90% of the overall amount of c-myc transcripts. The c-myc I expression is controlled primarily by two differentially regulated tandem promoters P1 and P2 which are separated by 50 bases. During oogenesis, maternal c-myc I mRNAs, are transcribed from both promoters whereas zygotic transcripts seem to initiate only from the P2 promoter. Sequence comparison between the promoter regions of c-myc I and II genes reveals the insertion in the c-myc I promoter region, between positions -831 and -389 relative to the P1 start site of a repetitive element. Comparison of X.laevis and mammalian c-myc promoter sequences reveals furthermore the conservation of cis-regulatory elements, including a motif known to be a negative regulator of the human c-myc transcription, a purine rich region, a binding site for the E2-F transcription factor and three SP1 binding sites. Finally, we report characterization of a new c-myc I mRNA which differ at the 5' end. Transcripts are possibly initiated at a putative alternative promoter located further upstream in the genome, and undergoes alternative splicing.
  Nucleic Acids Research 07/1991; 19(11):3081-8. · 8.03 Impact Factor