The recent availability of complete genome sequences is ushering in a new era in the analysis of gene regulation. The full genome sequence of the yeast Saccharomyces cerevisiae is ideal for such a study. Many yeast biochemical and genetic pathways are well understood, and its genome contains a manageable number of 5900 genes arranged in a compact fashion. We have extracted the sequences of all potential yeast promoters in order to study genes whose transcription is co-regulated during the yeast cell cycle. We search the literature for co-expressed genes, identify sequence motifs which are shared among the promoters of these genes using a statistical method called Gibbs sampling and by using word frequency methods, and then search for this sequence motif in other yeast promoters using a other statistical methods. Our first analysis is on the replication dependent histones which are transcribed during S phase. We have identified a sequence motif shared among the nine histone promoters, and have pinpointed other genes which contain copies of this motif. As it has been shown previously that this motif is partly responsible for the cell cycle dependent expression of histones, we predict that these other genes are co-regulated with the histones. We have extended this analysis to other cell cycle regulated genes in a project where data from a gene microarray experiment was used to identify genes which were co-expressed during the yeast cell cycle. Our predictions about cell cycle regulation will help to better characterize known genes, and lead to suggestions about the functions of yet-unstudied open reading frames. Furthermore, such work may result in a better understanding of the complex regulatory networks that orchestrate correct quantitative and temporal patterns of gene expression. We are also analyzing a large set of human promoters using several new techniques and statistics developed in this collaboration. A significant novelty of these developments is the use of promoters which are flush at the 3' end to the start of transcription allowing a set positional marker. In addition, data from ChIP-CHIP and ChIP-seq experiments are being included for analysis in order to further assess the role of chromatin organization and protein binding in transcription.

Agency
National Institute of Health (NIH)
Institute
National Library of Medicine (NLM)
Type
Intramural Research (Z01)
Project #
1Z01LM000084-11
Application #
7735074
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
11
Fiscal Year
2008
Total Cost
$379,346
Indirect Cost
Name
National Library of Medicine
Department
Type
DUNS #
City
State
Country
United States
Zip Code
Tharakaraman, Kannan; Bodenreider, Olivier; Landsman, David et al. (2008) The biological function of some human transcription factor binding motifs varies with position relative to the transcription start site. Nucleic Acids Res 36:2777-86
Polavarapu, Nalini; Marino-Ramirez, Leonardo; Landsman, David et al. (2008) Evolutionary rates and patterns for human transcription factor binding sites derived from repetitive DNA. BMC Genomics 9:226
Riz, I; Akimov, S S; Eaker, S S et al. (2007) TLX1/HOX11-induced hematopoietic differentiation blockade. Oncogene 26:4115-23
Tharakaraman, Kannan; Marino-Ramirez, Leonardo; Sheetlin, Sergey L et al. (2006) Scanning sequences after Gibbs sampling to find multiple occurrences of functional elements. BMC Bioinformatics 7:408
Marino-Ramirez, Leonardo; Jordan, I King; Landsman, David (2006) Multiple independent evolutionary solutions to core histone gene regulation. Genome Biol 7:R122
Tharakaraman, Kannan; Marino-Ramirez, Leonardo; Sheetlin, Sergey et al. (2005) Alignments anchored on genomic landmarks can aid in the identification of regulatory elements. Bioinformatics 21 Suppl 1:i440-8
Eriksson, Peter R; Mendiratta, Geetu; McLaughlin, Neil B et al. (2005) Global regulation by the yeast Spt10 protein is mediated through chromatin structure and the histone upstream activating sequence elements. Mol Cell Biol 25:9127-37
Marino-Ramirez, L; Lewis, K C; Landsman, D et al. (2005) Transposable elements donate lineage-specific regulatory sequences to host genomes. Cytogenet Genome Res 110:333-41
Marino-Ramirez, Leonardo; Spouge, John L; Kanga, Gavin C et al. (2004) Statistical analysis of over-represented words in human promoter sequences. Nucleic Acids Res 32:949-58
Fujibuchi, W; Anderson, J S; Landsman, D (2001) PROSPECT improves cis-acting regulatory element prediction by integrating expression profile data with consensus pattern searches. Nucleic Acids Res 29:3988-96

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