Xbp1-mediated repression of CLB gene expression contributes to the modifications of yeast cell morphology and cell cycle seen during nitrogen-limitedgrowth

Yeast cells undergo morphological transformations in response to diverse en vironmental signals. One such event, called pseudohyphal differentiation, o ccurs when diploid yeast cells are partially starved for nitrogen on a soli d agar medium. The nitrogen-starved cells elongate, and a small fraction fo rm filaments that penetrate the agar surface. The molecular basis for the c hanges in cell morphology and cell cycle in response to nitrogen limitation are poorly defined, in part because the heterogeneous growth states of par tially starved cells on agar media are not amenable to biochemical analysis . In this work, we used chemostat cultures to study the role of cell cycle regulators with respect to yeast differentiation in response to nitrogen li mitation under controlled, homogeneous culture conditions. We found that Cl b1, Clb2, and Clb5 cyclin levels are reduced in nitrogen-limited chemostat cultures compared to levels in rich-medium cultures, whereas the Xbp1 trans criptional repressor is highly induced under these conditions. Furthermore, the deletion of XBP1 prevents the drop in Clb2 levels and inhibits cellula r elongation in nitrogen-limited chemostat cultures as well as inhibiting p seudohyphal growth on nitrogen-limited agar media. Deletion of the CLB2 gen e restores an elongated morphology and filamentation to the xbp1 Delta muta nt in response to nitrogen limitation. Transcriptional activation of the XB P1 gene and the subsequent repression of CLB gene expression are thus key r esponses of yeast cells to nitrogen limitation.