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Nucleic Acids Research, 2000, Vol. 28, No. 16 3160-3167
© 2000 Oxford University Press

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

Mahmoud Elkhaimi, Mohan R. Kaadige, Deepa Kamath, John C. Jackson, Hector Biliran Jr and John M. Lopes*

Department of Biological Sciences, Wayne State University, 5047 Gullen Mall, Detroit, MI 48202, USA

The Ume6p–Sin3p–Rpd3p complex negatively regulates expression of genes containing a Ume6p binding site. However, these regulatory proteins also function independently to regulate gene expression both negatively and positively. The model system for this combinatorial regulation is the yeast phospholipid biosynthetic pathway. Sin3p negatively regulates the INO1, CHO1, CHO2 and 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 activator gene. Here, we demonstrate that the effect of Ume6p on INO2 gene expression is also indirect. We also show that Rpd3p is a negative regulator of phospholipid biosynthetic gene expression. The ability of Ume6p, Sin3p and Rpd3p to differentially regulate expression of the phospholipid biosynthetic genes affects phospholipid composition. A sin3 mutant strain lacks detectable levels of phosphatidylethanolamine and elevated levels of phosphatidylcholine (PC) and a rpd3 mutant strain has reduced levels of PC. These alterations in membrane composition suggest that there may exist additional differences in regulation of phospholipid biosynthetic gene expression and that membrane compositions may be coordinated with other biological processes regulated by Ume6p, Sin3p and Rpd3p.

* To whom correspondence should be addressed. Tel: +1 313 993 7816; Fax: +1 313 577 6891; Email: jlopes@sun.science.wayne.eduPresent address:John C. Jackson, Anheuser-Busch, Brewing Technical Services, 1 Busch Place (156-2), St Louis, MO 63118-1852, USA


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