The global transcriptional response to transient cell wall damage in Saccharomyces cerevisiae and its regulation by the cell integrity signaling pathway.
In the yeast Saccharomyces cerevisiae, environmental stress conditions that damage the cell wall lead to activation of the so-called "compensatory mechanism," aimed at preserving cell integrity through a remodeling of this extracellular matrix. Here we used DNA microarrays to investigate the molecular basis of this response to two agents that induce transient cell wall damage; namely Congo Red and Zymolyase. Treatment of the cells with these two agents elicited the up-regulation of 132 and 101 genes respectively, the main functional groups among them being involved in cell wall construction and metabolism. The main response does not occur until hours after exposure to the cell wall-perturbing agent. In some cases, this response was transient, but more sustained in others, especially in the case of the genes involved in cell wall remodeling. Clustering of these data together with those from the response to constitutive cell wall damage, revealed the existence of a cluster of co-regulated genes that was strongly induced under all conditions assayed. Those genes induced by cell wall damage showed an enrichment in DNA binding motifs for Rlm1p, Crz1p, SBF (Swi4p/Swi6p), Msn2p/Msn4p, Ste12p, and Tec1p transcription factors, suggesting a complex regulation of this response together with the possible involvement of several signaling pathways. With the exception of PHO89 and FKS2, none of the genes induced by Congo Red was up-regulated in a slt2 strain. Moreover, characterization of the transcriptional response to Congo Red in a rlm1 mutant strain revealed that only a few genes (i.e. PHO89, FKS2, YLR042C, and CHA1) were induced at least partially independently of the transcription factor Rlm1p, the rest being totally dependent on this transcription factor for their activation. Our findings consistently demonstrate that the cell integrity signaling pathway regulates the cell wall damage compensatory response, mainly through transcriptional activation mediated by Rlm1p.
García
Raúl
R
Departamento de Microbiología II, Facultad de Farmacia, Universidad Complutense de Madrid, 28040 Madrid, Spain. jarroyo@farm.ucm.es
Bermejo
Clara
C
Grau
Cecilia
C
Pérez
Rosa
R
Rodríguez-Peña
Jose Manuel
JM
Francois
Jean
J
Nombela
César
C
Arroyo
Javier
J
D000483:Alleles; D020816:Amino Acid Motifs; D015153:Blotting, Western; D002473:Cell Wall / Q000378:metabolism*; D003224:Congo Red / Q000494:pharmacology; D004247:DNA / Q000737:chemistry; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000378:metabolism; D017353:Gene Deletion; D006867:Hydrolases / Q000494:pharmacology; D007700:Kinetics; D026161:MADS Domain Proteins; D020411:Oligonucleotide Array Sequence Analysis; D016366:Open Reading Frames; D010641:Phenotype; D011401:Promoter Regions, Genetic; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins; D013997:Time Factors; D014157:Transcription Factors / Q000737:chemistry; D014158:Transcription, Genetic; D015533:Transcriptional Activation; D015854:Up-Regulation
D018076:DNA, Complementary; D026161:MADS Domain Proteins; C095725:RLM1 protein, S cerevisiae; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors; C037833:zymolyase; D003224:Congo Red; D012313:RNA; D004247:DNA; D006867:Hydrolases