Inferring yeast cell cycle regulators and interactions using transcription factor activities

Young-Lyeol Yang; Suen, Jason; Brynildsen, Mark P; Galbraith, Simon J; Liao, James C
January 2005
BMC Genomics;2005, Vol. 6, p90
Academic Journal
Background: Since transcription factors are often regulated at the post-transcriptional level, their activities, rather than expression levels may provide valuable information for investigating functions and their interactions. The recently developed Network Component Analysis (NCA) and its generalized form (gNCA) provide a robust framework for deducing the transcription factor activities (TFAs) from various types of DNA microarray data and transcription factor-gene connectivity. The goal of this work is to demonstrate the utility of TFAs in inferring transcription factor functions and interactions in Saccharomyces cerevisiae cell cycle regulation. Results: Using gNCA, we determined 74 TFAs from both wild type and fkh1 fkh2 deletion mutant microarray data encompassing 1529 ORFs. We hypothesized that transcription factors participating in the cell cycle regulation exhibit cyclic activity profiles. This hypothesis was supported by the TFA profiles of known cell cycle factors and was used as a basis to uncover other potential cell cycle factors. By combining the results from both cluster analysis and periodicity analysis, we recovered nearly 90% of the known cell cycle regulators, and identified 5 putative cell cycle-related transcription factors (Dal81, Hap2, Hir2, Mss11, and Rlm1). In addition, by analyzing expression data from transcription factor knockout strains, we determined 3 verified (Ace2, Ndd1, and Swi5) and 4 putative interaction partners (Cha4, Hap2, Fhl1, and Rts2) of the forkhead transcription factors. Sensitivity of TFAs to connectivity errors was determined to provide confidence level of these predictions. Conclusion: By subjecting TFA profiles to analyses based upon physiological signatures we were able to identify cell cycle related transcription factors consistent with current literature, transcription factors with potential cell cycle dependent roles, and interactions between transcription factors.


Related Articles

  • Involvement of calcineurin-dependent degradation of Yap1p in Ca2+-induced G2 cell-cycle regulation in Saccharomyces cerevisiae. Yokoyama, Hiroshi; Mizunuma, Masaki; Okamoto, Michiyo; Yamamoto, Josuke; Hirata, Dai; Miyakawa, Tokichi // EMBO Reports;May2006, Vol. 7 Issue 5, p519 

    The Ca2+-activated pathways in Saccharomyces cerevisiae induce a delay in the onset of mitosis through the activation of Swe1p, a negative regulatory kinase that inhibits the Cdc28p/Clb complex. We isolated the YAP1 gene as a multicopy suppressor of calcium sensitivity owing to the loss of ZDS1,...

  • Properties of a sucrose-tolerant Mutant of Saccharomyces cerevisiae. Takahiro Oba; Hikaru Suenaga; Shigeru Muta; Kosuke Tashiro; Satoru Kuhara // World Journal of Microbiology & Biotechnology;Jul2008, Vol. 24 Issue 7, p1233 

    Abstract  We characterized a sucrose-tolerant mutant of Saccharomyces cerevisiae, S22, that produces about four times as much acetate as the wild-type strain K9. We monitored the concentration of extracellular acetate during cultivation, and compared the gene expression ratios of S22 with...

  • Detecting Periodic Genes from Irregularly Sampled Gene Expressions: A Comparison Study. Wentao Zhao; Agyepong, Kwadwo; Serpedin, Erchin; Dougherty, Edward R. // EURASIP Journal on Bioinformatics & Systems Biology;2008, Special section p1 

    Time series microarray measurements of gene expressions have been exploited to discover genes involved in cell cycles. Due to experimental constraints, most microarray observations are obtained through irregular sampling. In this paper three popular spectral analysis schemes, namely,...

  • Identification of temporal association rules from time-series microarray data sets. Hojung Nam; KiYoung Lee; Doheon Lee // BMC Bioinformatics;2009 Supplement 3, Vol. 10, Special section p1 

    Background: One of the most challenging problems in mining gene expression data is to identify how the expression of any particular gene affects the expression of other genes. To elucidate the relationships between genes, an association rule mining (ARM) method has been applied to microarray...

  • Single-cell proteomic analysis of S. cerevisiae reveals the architecture of biological noise. Newman, John R. S.; Ghaemmaghami, Sina; Ihmels, Jan; Breslow, David K.; Noble, Matthew; DeRisi, Joseph L.; Weissman, Jonathan S. // Nature;6/15/2006, Vol. 441 Issue 7095, p840 

    A major goal of biology is to provide a quantitative description of cellular behaviour. This task, however, has been hampered by the difficulty in measuring protein abundances and their variation. Here we present a strategy that pairs high-throughput flow cytometry and a library of GFP-tagged...

  • Regulation of megakaryocytic differentiation of K562 cells by FosB, a member of the Fos family of AP-1 transcription factors. Limb, J.-K.; Yoon, S.; Lee, K. E.; Kim, B.-H.; Lee, S.; Bae, Y. S.; Jhon, G.-J.; Kim, J. // Cellular & Molecular Life Sciences;Jun2009, Vol. 66 Issue 11/12, p1962 

    The regulation of megakaryocytic differentiation is poorly understood. Using K562 cells, which can partly recapitulate the process in response to phorbol 12-myristate 13-acetate (PMA), we performed microarray-based gene expression profiling to identify genes that play significant roles in...

  • Systematic identification of cell cycle regulated transcription factors from microarray time series data. Chao Cheng; Li, Lei M. // BMC Genomics;2008, Vol. 9, Special section p1 

    Background: The cell cycle has long been an important model to study the genome-wide transcriptional regulation. Although several methods have been introduced to identify cell cycle regulated genes from microarray data, they can not be directly used to investigate cell cycle regulated...

  • The Yak1 Protein Kinase Lies at the Center of a Regulatory Cascade Affecting Adhesive Growth and Stress Resistance in Saccharomyces cerevisiae. Malcher, Mario; Schladebeck, Sarah; Mösch, Hans-Ulrich // Genetics;Mar2011, Vol. 187 Issue 3, p717 

    In Saccharomyces cerevisiae, adhesive growth on solid surfaces is mediated by the flocculin Flo11 to confer biofilm and filament formation. Expression of FLO11 is governed by a complex regulatory network that includes, e.g., the protein kinase A (PKA) signaling pathway. In addition, numerous...

  • Control of the C. albicans Cell Wall Damage Response by Transcriptional Regulator Cas5. Bruno, Vincent M.; Kalachikov, Sergey; Subaran, Ryan; Nobile, Clarissa J.; Kyratsous, Christos; Mitchell, Aaron P. // PLoS Pathogens;Mar2006, Vol. 2 Issue 3, pe21 

    The fungal cell wall is vital for growth, development, and interaction of cells with their environment. The response to cell wall damage is well understood from studies in the budding yeast Saccharomyces cerevisiae, where numerous cell wall integrity (CWI) genes are activated by transcription...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics