Transcriptional control of phosphate-regulated genes in yeast: the role of specific transcription factors and chromatin remodeling complexes in vivo

摘要

Gene specific regulation of transcription is of fundamental importance to cell survival. When the yeast, Saccharomyces cerevisiae is challenged by growth under conditions of nutrient limitation the cell must respond rapidly to stimulate expression of the necessary gene products and thus efficiently counter this environmental stress. The PHO system of yeast is an example of such a regulatory pathway. It contains several phosphatases and permeases the expression of which being determined by the phosphate concentration of the growth medium. In phosphate containing medium the transcription of these genes is prohibited by the negative regulation of the PHO specific transactivator Pho4. These repressing conditions witness the phosphorylation of Pho4 by the Pho80-Pho85 cyclin-CDK complex and its subsequent Msn5 dependent export from the nucleus, thus spatially precluding transcription. Under conditions of phosphate limitation the activity of the Pho80-Pho85 complex is blocked through the action of the cyclin-CDK inhibitor, Pho81, leading to the accumulation of unphosphorylated Pho4 in the nucleus and hence transcriptional activation of PHO specific genes such as PHO5 and PHO8. Pho4 brings about gene activation in a co-operative manner with the pleiotropic factor Pho2. Phosphorylation of Pho4 also serves to prevent this protein-protein interaction, and thus regulate the activation potential of Pho4 at a second level. finally, to bring about the activation of transcription Pho4 must effectively challenge the repressive chromatin structures found in the promoter of its target genes. To alleviate this repression the cell has evolved dedicated complexes which locally alter the structure of chromatin, thus facilitating gene specific release from nucleosomal repression. Thus the PHO system provides an ideal model for the study of the interplay between gene specific transcription factors and chromatin modifying complexes in the regulation of transcription.