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D Marechal

Publications and source records attributed to D Marechal.

7 recordsLinked to original sources
PubMed2001

NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans.

We have characterized CaNrg1 from Candida albicans, the major fungal pathogen in humans. CaNrg1 contains a zinc finger domain that is conserved in transcriptional regulators from fungi to humans. It is most closely related to ScNrg1, which represses transcription in a Tup1-dependent fashion in Saccharomyces cerevisiae. Inactivation of CaNrg1 in C.albicans causes filamentous and invasive growth, derepresses hypha-specific genes, increases sensitivity to some stresses and attenuates virulence. A tup1 mutant displays similar phenotypes. However, unlike tup1 cells, nrg1 cells can form normal hyphae, generate chlamydospores at normal rates and grow at 42 degrees C. Transcript profiling of 2002 C.albicans genes reveals that CaNrg1 represses a subset of CaTup1-regulated genes, which includes known hypha-specific genes and other virulence factors. Most of these genes contain an Nrg1 response element (NRE) in their promoter. CaNrg1 interacts specifically with an NRE in vitro. Also, deletion of two NREs from the ALS8 promoter releases it from Nrg1-mediated repression. Hence, CaNrg1 is a transcriptional repressor that appears to target CaTup1 to a distinct set of virulence-related functions, including yeast-hypha morphogenesis.

Amino Acid Sequence↗
PubMed2001

Transcript profiling in Candida albicans reveals new cellular functions for the transcriptional repressors CaTup1, CaMig1 and CaNrg1.

The pathogenic fungus, Candida albicans contains homologues of the transcriptional repressors ScTup1, ScMig1 and ScNrg1 found in budding yeast. In Saccharomyces cerevisiae, ScMig1 targets the ScTup1/ScSsn6 complex to the promoters of glucose repressed genes to repress their transcription. ScNrg1 is thought to act in a similar manner at other promoters. We have examined the roles of their homologues in C. albicans by transcript profiling with an array containing 2002 genes, representing about one quarter of the predicted number of open reading frames (ORFs) in C. albicans. The data revealed that CaNrg1 and CaTup1 regulate a different set of C. albicans genes from CaMig1 and CaTup1. This is consistent with the idea that CaMig1 and CaNrg1 target the CaTup1 repressor to specific subsets of C. albicans genes. However, CaMig1 and CaNrg1 repress other C. albicans genes in a CaTup1-independent fashion. The targets of CaMig1 and CaNrg1 repression, and phenotypic analyses of nrg1/nrg1 and mig1/mig1 mutants, indicate that these factors play differential roles in the regulation of metabolism, cellular morphogenesis and stress responses. Hence, the data provide important information both about the modes of action of these transcriptional regulators and their cellular roles. The transcript profiling data are available at http://www.pasteur.fr/recherche/unites/RIF/transcriptdata/.

Candida albicans↗
PubMed1999

Cloning of breakpoints in and downstream the IGF2 gene that are associated with overexpression of IGF2 transcripts in colorectal tumours.

The human IGF2 gene belongs to a group of imprinted genes clustered on the short arm of chromosome 11, band p15.5. It contains 9 exons and spans over 30 kb. IGF2 mRNA overexpression has been reported in human tumours and in some inherited growth disorders. It was recently demonstrated that IGF2 mRNA overexpression contributes to tumour progression and that loss of parental imprinting as well as altered transcription factors are contributing to this overexpression. We have reported structural alterations in the 3' region of the IGF2 gene in two colorectal tumours that overexpressed the IGF2 transcript by 200- and 800-fold. We cloned by the vectorette-PCR strategy, genomic DNA fragments containing the breakpoints from these tumours. The sequencing of these fragments positioned the breakpoint 2 kb downstream the IGF2 gene in one tumour, and in exon 9 in the second. Both breakpoints occurred in regions containing repetitive elements: a TGGA repeat we have identified downstream the gene, and the (CA)n repetition in exon 9. We hypothesize that a negative regulatory element, located downstream the IGF2 gene, has been deleted following these structural alterations and leads to IGF2 gene overexpression.

Chromosome Aberrations↗
PubMed1994

Towards a pharmacological approach of Alzheimer's disease based on the molecular biology of the amyloid precursor protein (APP).

After heart disease, cancer and stroke, Alzheimer's disease (AD) is the fourth major cause of death in the developed countries. Due to demographic changes, this situation will further worsen in the future. With the use of molecular biology techniques, important progress has recently been made in the understanding of the molecular changes leading to some forms of this disabling illness. The first step was the partial sequencing of the amyloid protein accumulating in the senile plaques and vascular deposits characteristic of AD. This allowed the cloning of a cDNA coding for a long amyloid precursor protein (APP). During the last few years, independent reports have described the presence of several reproducible point mutations in specific codons of APP in early onset familial Alzheimer patients. These mutations are responsible for an abnormal processing of APP, leading to the formation of pathological beta/A4 amyloid deposits. beta/A4 has been shown to possess neurotrophic properties in embryonic neurones and to be a potent neurotoxic agent in differentiated hippocampal neurones. More recently, modifications of intracellular calcium, activation of kinases, free radical generation and anomalies in potassium channels have been described as possible mechanisms of beta/A4 toxicity. Some forms of Apo-E lipoprotein may be an additional risk factor. Hence, it now seems possible to elaborate a coherent theory to explain the cascade of events leading to the development of AD. Genetically induced point mutations or environmental factors may produce a modification of the APP metabolism and processing. As a consequence, abnormal deposits of beta/A4 are formed. They may exert direct or indirect neurotoxic actions. A degeneration of cholinergic, catecholaminergic and other neurones follows, leading to the well known cognitive and behavioural changes of AD.

Alzheimer Disease↗
PubMed1989

[Study of new brain peptides using genetic engineering methods].

Using the methods of molecular biology, we have been able to clone 5 rat brain specific cDNAs coding for brain specific proteins. The partial sequencing of the first of those clones gave no homology with the genes contained in Genebank and EMBL data bank. In the future, we intend to look for a possible effect of those brain specific proteins on the neuronal activity of rat brain neurons.

DNA, Circular↗
PubMed1988

Cloning and partial sequencing of a new rat brain specific cDNA.

In order to find brain specific transcripts in a pUC13 cDNA library prepared from rat brain cytoplasmic poly(A)+ RNAs, the following steps were observed: 1. Randomly chosen cDNA clones from the brain library were screened by radiolabelled single stranded cDNAs (sscDNAs) prepared from liver, spleen, kidney and intestine mRNAs. 2. The brain clones containing genetic information shared with the peripheral organs were discarded. 3. After hybridization of the remaining clones with radiolabelled sscDNAs prepared from rat brain poly(A)+ RNAs, 210 possibly brain specific clones were selected. 4. Plasmids containing cDNA of each of these clones were purified and after estimation of their cDNA sizes, clones containing inserts of at least 500 base pairs (bp) were used as radiolabelled probes against rat brain, liver, spleen, kidney and intestine poly(A)+ RNAs spotted onto nitrocellulose filters (dot blot analysis). 5. By using this screening procedure, several brain specific clones were obtained. One of them (clone III 25) is presently subjected to sequencing in M13 phage. 6. A computer analysis of the partial sequence so far obtained gives no significant homology to the 15.000 genes contained in Genebank and EMBL data bank. It seems therefore that we have isolated a new brain specific cDNA coding for a not yet described peptide.

Animals↗