Biomedical subjects

Philippe Marc

Publications and source records attributed to Philippe Marc.

5 recordsLinked to original sources

PubMed2003

A general strategy to uncover transcription factor properties identifies a new regulator of drug resistance in yeast.

We demonstrate a genomewide approach to determine the physiological role of a putative transcription factor, Ylr266, identified through yeast genome sequencing program. We constructed activated forms of the zinc finger (Zn(2)Cys(6)) protein Ylr266, and we analyzed the corresponding transcriptomes with DNA microarrays to characterize the up-regulated genes. The direct target genes of Ylr266 were further identified by in vivo chromatin immunoprecipitation procedure. The functions of the genes directly controlled by YLR266c are in agreement with the observed drug-resistance phenotype of the cell expressing an activated form of Ylr266. These target genes code for ATP-binding cassette or major facilitator superfamily transporters such as PDR15, YOR1, or AZR1 or for other proteins such as SNG1, YJL216c, or YLL056c which are already known to be involved in the yeast pleiotropic drug resistance (PDR) phenomenon. YLR266c could thus be named PDR8. Overlaps with the other PDR networks argue in favor of a new specific role for PDR8 in connection with the well known PDR regulators PDR1/PDR3 and YRR1. This strategy to identify the regulatory properties of an anonymous transcription factor is likely to be generalized to all the Zn(2)Cys(6) transcription factors from Saccharomyces cerevisiae and related yeasts.

Drug Resistance, Microbial↗

PubMed2002

Genome-wide analysis of mRNAs targeted to yeast mitochondria.

It is agreed that nuclear-encoded mitochondrial proteins are post-translationally targeted to mitochondria, even if, in some cases, a co-translational phase can assist the import of precursor proteins. We used yeast DNA microarrays to analyse the mRNA populations associated with free and mitochondrion-bound polysomes. As expected, many mRNAs, known to encode mitochondrial proteins, are localized to free cytoplasmic polysomes, but many are localized to mitochondrion-bound polysomes. Furthermore, the 3'-UTR of six randomly chosen mitochondrion-bound mRNAs contains sufficient information to target, in vivo, non-translatable RNA to the vicinity of mitochondria. Interestingly, genes producing mRNAs that are targeted to mitochondria are mainly of ancient bacterial origin, whereas those producing mRNAs that are translated in the cytoplasm are mainly of eukaryotic origin. These observations, which support the recent hypotheses concerning the dual origin of the mitochondrial proteome, provide new insights into the biogenesis of mitochondria.

DNA, Mitochondrial↗

PubMed2002

yMGV: helping biologists with yeast microarray data mining.

yMGV (yeast Microarray Global Viewer) was designed to provide biologists with meaningful information from genome-wide yeast expression data. The database includes most of the available expression data published on yeast microarrays over the last 4 years. It provides customizable tools for the rapid visualization of expression profiles associated with a set of genes from all published experiments. It also allows users to compare the results from different publications so that they can identify genes with common expression profiles. We used yMGV to perform global analyses to find a gene expression profile specific for given biological conditions and to locate functional gene clusters on chromosomes. Other organisms will be added to this database. yMGV is accessible on the web at http://transcriptome.ens.fr/ymgv.

Computer Graphics↗

PubMed2002

Arrayplot for visualization and normalization of cDNA microarray data.

UNLABELLED: Arrayplot is an application which allows filtering, visualization and normalization of raw cDNA microarray data. AVAILABILITY: MS-Windows binaries are freely available for non-profit use at http://www.biologie.ens.fr/yeast-publi.html. SUPPLEMENTARY INFORMATION: Scripts for online creation of Arrayplot files are available at http://transcriptome.ens.fr/lgm_bioinfo/

Computational Biology↗

PubMed2002

New insights into the pleiotropic drug resistance network from genome-wide characterization of the YRR1 transcription factor regulation system.

Yrr1p is a recently described Zn(2)Cys(6) transcription factor involved in the pleiotropic drug resistance (PDR) phenomenon. It is controlled in a Pdr1p-dependent manner and is autoregulated. We describe here a new genome-wide approach to characterization of the set of genes directly regulated by Yrr1p. We found that the time-course production of an artificial chimera protein containing the DNA-binding domain of Yrr1p activated the 15 genes that are also up-regulated by a gain-of-function mutant of Yrr1p. Gel mobility shift assays showed that the promoters of the genes AZR1, FLR1, SNG1, YLL056C, YLR346C, and YPL088W interacted with Yrr1p. The putative consensus Yrr1p binding site deduced from these experiments, (T/A)CCG(C/T)(G/T)(G/T)(A/T)(A/T), is strikingly similar to the PDR element binding site sequence recognized by Pdr1p and Pdr3p. The minor differences between these sequences are consistent with Yrr1p and Pdr1p and Pdr3p having different sets of target genes. According to these data, some target genes are directly regulated by Pdr1p and Pdr3p or by Yrr1p, whereas some genes are indirectly regulated by the activation of Yrr1p. Some genes, such as YOR1, SNQ2, and FLR1, are clearly directly controlled by both classes of transcription factor, suggesting an important role for the corresponding membrane proteins.

Amino Acid Sequence↗