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Genome-wide co-occurrence of promoter elements reveals a cis-regulatory cassette of rRNA transcription motifs in S. cerevisiae

Genome Research (in press)




Priya Sudarsanam*
Yitzhak (Tzachi) Pilpel*
George M. Church
*These authors made equal contributions to this work

Department of Genetics, Harvard Medical School, and
Lipper Center for Computational Genetics


Abstract
Figures
 Tables
Data & Resources
Contacts for comments


Abstract

Combinatorial regulation is an important feature of eukaryotic transcription. However, only a limited number of studies have characterized this aspect on a whole-genome level. We have conducted a genome-wide computational survey to identify cis-regulatory motif pairs that co-occur in a significantly high number of promoters in the S. cerevisiae genome. A pair of novel motifs, mRRPE and PAC, co-occur most highly in the genome, primarily in the promoters of genes involved in rRNA transcription and processing. The two motifs show significant positional and orientational bias with mRRPE being closer to the ATG than PAC in most promoters. Two additional rRNA-related motifs, mRRSE3 and mRRSE10, also co-occur with mRRPE and PAC. mRRPE and PAC are the primary determinants of expression profiles while mRRSE3 and mRRSE10 modulate these patterns. We describe a new computational approach for studying the functional significance of the physical locations of promoter elements that uses combined analyses of genome sequence and microarray data. Applying this methodology to the regulatory cassette containing the four rRNA motifs demonstrates that the relative promoter locations of these elements have a profound effect on the expression patterns of the downstream genes. These findings provide a function for these novel motifs and insight into the mechanism by which they regulate gene expression. The methodology introduced here should prove particularly useful for analyzing transcriptional regulation in more complex genomes.

Figures


 

Positional Combinograms


Positional Combinogram for sporulation

Combinograms of rRNA transcription genes


rRNA transcription genes in DNA-damage
rRNA transcription genes in DNA-damage
 

Tables

1) Our full collection of 356 known and putative promoter element motifs
2) The MIPS rRNA synthesis set of ORFs (used to derived motifs m_RRSE3 and m_rRSE10 )
3) The MIPS rRNA processing set of ORFs (used to derived motifs PAC and mRRPE)
4) Also, please view here a Fasta formatted file with the up-stream regions of all ORFs in the genome
(provided by Jason Hughes, and used by AlignACE to derive motifs from the respective MIPS categories)

Data & Resources


All expression data were taken from ExpressDB

Motifs were derived using AlignACE and matched to promoters in the genome using ScanACE
 


Contacts


Correspondence may be addressed to George M. Church at:
Department of Genetics,
Harvard Medical School
200 Longwood Avenue,
Boston, MA 02115 USA
fax (617) 432-7266
Or Email to:
Tzachi Pilpel Priya Sudarsanam George Church