Genome-wide analysis of gene expression relationships in transcriptional regulatory networks

From merging a number of data sources, we created an extensive map of the transcriptional regulatory network in yeast, comprising 7419 interactions connecting 180 transcription factors (TFs) with their target genes. We integrated this network with gene-expression data, relating the expression profiles of TFs and target genes. We found that genes targeted by the same TF tend to be co-expressed, with the degree of co-expression increasing if genes share more than one TF. Moreover, shared targets of a TF tend to have similar cellular functions. In contrast, the expression relationships between the TFs and their targets are much more complicated, often exhibiting time-shifted or inverted behavior.

[1]  M. Gerstein,et al.  Complex transcriptional circuitry at the G1/S transition in Saccharomyces cerevisiae. , 2002, Genes & development.

[2]  D. Botstein,et al.  Genomic expression responses to DNA-damaging agents and the regulatory role of the yeast ATR homolog Mec1p. , 2001, Molecular biology of the cell.

[3]  Peter C. Hollenhorst,et al.  Mechanisms controlling differential promoter-occupancy by the yeast forkhead proteins Fkh1p and Fkh2p: implications for regulating the cell cycle and differentiation. , 2001, Genes & development.

[4]  D. Botstein,et al.  Genomic binding sites of the yeast cell-cycle transcription factors SBF and MBF , 2001, Nature.

[5]  D. Botstein,et al.  Genomic expression programs in the response of yeast cells to environmental changes. , 2000, Molecular biology of the cell.

[6]  D. Botstein,et al.  Two yeast forkhead genes regulate the cell cycle and pseudohyphal growth , 2000, Nature.

[7]  Lukas Endler,et al.  Forkhead-like transcription factors recruit Ndd1 to the chromatin of G2/M-specific promoters , 2000, Nature.

[8]  O. Stemmann,et al.  A putative protein complex consisting of Ctf19, Mcm21, and Okp1 represents a missing link in the budding yeast kinetochore. , 1999, Genes & development.

[9]  David Lydall,et al.  NDD1, a High-Dosage Suppressor ofcdc28-1N, Is Essential for Expression of a Subset of Late-S-Phase-Specific Genes in Saccharomyces cerevisiae , 1999, Molecular and Cellular Biology.

[10]  N. Roy,et al.  MCM21 and MCM22, two novel genes of the yeast Saccharomyces cerevisiae are required for chromosome transmission , 1999, Molecular microbiology.

[11]  D. Botstein,et al.  Cluster analysis and display of genome-wide expression patterns. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[12]  Michael Ruogu Zhang,et al.  Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. , 1998, Molecular biology of the cell.

[13]  D. Botstein,et al.  The transcriptional program of sporulation in budding yeast. , 1998, Science.

[14]  N. Grandin,et al.  The Cdc14 phosphatase is functionally associated with the Dbf2 protein kinase in Saccharomycescerevisiae , 1998, Molecular and General Genetics MGG.

[15]  P. Brown,et al.  Exploring the metabolic and genetic control of gene expression on a genomic scale. , 1997, Science.

[16]  D. J. Stillman,et al.  Identification of the Saccharomyces cerevisiae genes STB1–STB5 encoding Sin3p binding proteins , 1997, Molecular and General Genetics MGG.

[17]  James L. Winkler,et al.  Accessing Genetic Information with High-Density DNA Arrays , 1996, Science.

[18]  G. Natsoulis,et al.  SPT10 and SPT21 are required for transcription of particular histone genes in Saccharomyces cerevisiae , 1994, Molecular and cellular biology.

[19]  John J. Wyrick,et al.  Genome-wide location and function of DNA binding proteins. , 2000, Science.

[20]  Hans-Werner Mewes,et al.  MIPS: a database for protein sequences, homology data and yeast genome information , 1997, Nucleic Acids Res..