Combinatorial regulation of phospholipid biosynthetic gene expression by the UME6, SIN3 and RPD3 genes

The Ume6p-Sin3p-Rpd3p complex negatively regulates expression of genes cont aining a Ume6p binding site. However, these regulatory proteins also functi on independently to regulate gene expression both negatively and positively . The model system for this combinatorial regulation is the yeast phospholi pid biosynthetic pathway. Sin3p negatively regulates the INO1, CHO1, CHO2 a nd OPI3 genes while Ume6p negatively regulates the INO1 gene and positively regulates the other genes, We have suggested that the positive regulation results from indirect effects on expression of the INO2 transcriptional act ivator gene. Here, we demonstrate that the effect of Ume6p on INO2 gene exp ression is also indirect. We also show that Rpd3p is a negative regulator o f phospholipid biosynthetic gene expression. The ability of Ume6p, Sin3p an d Rpd3p to differentially regulate expression of the phospholipid biosynthe tic genes affects phospholipid composition. A sin3 mutant strain tacks dete ctable levels of phosphatidylethanolamine and elevated levels of phosphatid ylcholine (PC) and a rpd3 mutant strain has reduced revels of PC. These alt erations in membrane composition suggest that there may exist additional di fferences in regulation of phospholipid biosynthetic gene expression and th at membrane compositions may be coordinated with other biological processes regulated by Ume6p, Sin3p and Rpd3p.