期刊
MOLECULAR BIOLOGY OF THE CELL
卷 23, 期 15, 页码 3008-3024出版社
AMER SOC CELL BIOLOGY
DOI: 10.1091/mbc.E12-03-0233
关键词
-
类别
资金
- National Institute of General Medical Sciences Center for Quantitative Biology Grant [GM071508]
- National Institutes of Health Grant [GM046406, HG003008]
- Ruth Kirschstein Cancer Training Grant [T32 CA-009528]
- National Science Foundation Graduate Research Fellowship
- John Simon Guggenheim Foundation Fellowship
Methionine abundance affects diverse cellular functions, including cell division, redox homeostasis, survival under starvation, and oxidative stress response. Regulation of the methionine biosynthetic pathway involves three DNA-binding proteins-Met31p, Met32p, and Cbf1p. We hypothesized that there exists a division of labor among these proteins that facilitates coordination of methionine biosynthesis with diverse biological processes. To explore combinatorial control in this regulatory circuit, we deleted CBF1, MET31, and MET32 individually and in combination in a strain lacking methionine synthase. We followed genome-wide gene expression as these strains were starved for methionine. Using a combination of bioinformatic methods, we found that these regulators control genes involved in biological processes downstream of sulfur assimilation; many of these processes had not previously been documented as methionine dependent. We also found that the different factors have overlapping but distinct functions. In particular, Met31p and Met32p are important in regulating methionine metabolism, whereas p functions as a generalist transcription factor that is not specific to methionine metabolism. In addition, Met31p and Met32p appear to regulate iron-sulfur cluster biogenesis through direct and indirect mechanisms and have distinguishable target specificities. Finally, CBF1 deletion sometimes has the opposite effect on gene expression from MET31 and MET32 deletion.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据