SCPD: a promoter database of the yeast Saccharomyces cerevisiae.
ABSTRACT In order to facilitate a systematic study of the promoters and transcriptionally regulatory cis-elements of the yeast Saccharomyces cerevisiae on a genomic scale, we have developed a comprehensive yeast-specific promoter database, SCPD.
Currently SCPD contains 580 experimentally mapped transcription factor (TF) binding sites and 425 transcriptional start sites (TSS) as its primary data entries. It also contains relevant binding affinity and expression data where available. In addition to mechanisms for promoter information (including sequence) retrieval and a data submission form, SCPD also provides some simple but useful tools for promoter sequence analysis.
SCPD can be accessed from the URL http://cgsigma.cshl.org/jian. The database is continually updated.
- SourceAvailable from: oxfordjournals.org[show abstract] [hide abstract]
ABSTRACT: The systematic sequencing of the yeast genome reveals the presence of many potential genes of unknown function. One way to approach their function is to define which regulatory system controls their transcription. This can also be accomplished by the detection of an upstream activation sequence (UAS). Such a detection can be done by computer, provided that the definition of a UAS includes sufficient and precise rules. We have established such rules for the UASs of the GAL4, RAP1 (RPG box), GCN4, and the HAP2/HAP3/HAP4 regulatory proteins, as well as for a motif (PAC) frequently found upstream of the genes of the RNA polymerase A and C subunits. These rules were applied to the chromosome III DNA sequence, and gave precise predictions.Computer applications in the biosciences: CABIOS 11/1996; 12(5):363-74.
- [show abstract] [hide abstract]
ABSTRACT: Transcription initiation by RNA polymerase II (RNA pol II) requires interaction between cis-acting promoter elements and trans-acting factors. The eukaryotic promoter consists of core elements, which include the TATA box and other DNA sequences that define transcription start sites, and regulatory elements, which either enhance or repress transcription in a gene-specific manner. The core promoter is the site for assembly of the transcription preinitiation complex, which includes RNA pol II and the general transcription fctors TBP, TFIIB, TFIIE, TFIIF, and TFIIH. Regulatory elements bind gene-specific factors, which affect the rate of transcription by interacting, either directly or indirectly, with components of the general transcriptional machinery. A third class of transcription factors, termed coactivators, is not required for basal transcription in vitro but often mediates activation by a broad spectrum of activators. Accordingly, coactivators are neither gene-specific nor general transcription factors, although gene-specific coactivators have been described in metazoan systems. Transcriptional repressors include both gene-specific and general factors. Similar to coactivators, general transcriptional repressors affect the expression of a broad spectrum of genes yet do not repress all genes. General repressors either act through the core transcriptional machinery or are histone related and presumably affect chromatin function. This review focuses on the global effectors of RNA polymerase II transcription in yeast, including the general transcription factors, the coactivators, and the general repressors. Emphasis is placed on the role that yeast genetics has played in identifying these factors and their associated functions.Microbiology and Molecular Biology Reviews 07/1998; 62(2):465-503. · 16.42 Impact Factor
- [show abstract] [hide abstract]
ABSTRACT: Optimized weight matrices defining four major eukaryotic promoter elements, the TATA-box, cap signal, CCAAT-, and GC-box, are presented; they were derived by comparative sequence analysis of 502 unrelated RNA polymerase II promoter regions. The new TATA-box and cap signal descriptions differ in several respects from the only hitherto available base frequency Tables. The CCAAT-box matrix, obtained with no prior assumption but CCAAT being the core of the motif, reflects precisely the sequence specificity of the recently discovered nuclear factor NY-I/CP1 but does not include typical recognition sequences of two other purported CCAAT-binding proteins, CTF and CBP. The GC-box description is longer than the previously proposed consensus sequences but is consistent with Sp1 protein-DNA binding data. The notion of a CACCC element distinct from the GC-box seems not to be justified any longer in view of the new weight matrix. Unlike the two fixed-distance elements, neither the CCAAT- nor the GC-box occurs at significantly high frequency in the upstream regions of non-vertebrate genes. Preliminary attempts to predict promoters with the aid of the new signal descriptions were unexpectedly successful. The new TATA-box matrix locates eukaryotic transcription initiation sites as reliably as do the best currently available methods to map Escherichia coli promoters. This analysis was made possible by the recently established Eukaryotic Promoter Database (EPD) of the EMBL Nucleotide Sequence Data Library. In order to derive the weight matrices, a novel algorithm has been devised that is generally applicable to sequence motifs positionally correlated with a biologically defined position in the sequences. The signal must be sufficiently over-represented in a particular region relative to the given site, but need not be present in all members of the input sequence collection. The algorithm iteratively redefines the set of putative motif representatives from which a weight matrix is derived, so as to maximize a quantitative measure of local over-representation, an optimization criterion that naturally combines structural and positional constancy. A comprehensive description of the technique is presented in Methods and Data.Journal of Molecular Biology 05/1990; 212(4):563-78. · 3.91 Impact Factor
SCPD: a promoter database of the yeast
???? ??? ??? ??????? ?? ?????
???? ?????? ?????? ??????????? ?? ??? ???? ? ???????? ????? ???? ?????? ???????
?? ?????? ???
???????? ?? ??????? ?? ????? ??????? ?? ???????? ??? ????? ???????? ?? ???????? ?? ????
Motivation: In order to facilitate a systematic study of the
promoters and transcriptionally regulatory cis-elements of the
yeast Saccharomyces cerevisiae on a genomic scale, we have
developed a comprehensive yeast-specific promoter database,
Results: Currently SCPD contains 580 experimentally mapped
transcription factor (TF) binding sites and 425 transcriptional
start sites (TSS) as its primary data entries. It also contains
relevant binding affinity and expression data where available.
In addition to mechanisms for promoter information (including
sequence) retrieval and a data submission form, SCPD also
provides some simple but useful tools for promoter sequence
Availability: SCPD can be accessed from the URL http://cgsig-
ma.cshl.org/jian. The database is continually updated.
Contact: email@example.com or firstname.lastname@example.org
The complete genomic sequence of the yeast Saccharomyces
cerevisiae reveals >6000 open reading frames (ORFs).
About 3000 have been assigned functions (Goffeau et al.,
1996). The transcription is largely controlled and regulated
by their promoter region located upstream of the coding re-
gions (e.g. Hampsey, 1998). There are ∼200 known yeast
transcription factors including activators/repressors and co-
activators/co-repressors, in addition to basal factors.
The availability of the complete genome enables large-
scale functional studies using DNA microarray and oligo-
nucleotide chip technologies, in which the expression pattern
of >6000 genes can be simultaneously monitored (DeRisi et
al., 1997). To facilitate the gene regulation analysis of the
large-scale expression data, it is imperative to build a data-
base representing the current knowledge of yeast promoters.
We constructed SCPD, a promoter database of the yeast
S.cerevisiae. Since SCPD is based on published results of
individual genes, it can be used either to complement or sub-
stantiate large-scale genomic expression data. Furthermore,
its information on conserved sequence patterns of transcrip-
tion factor (TF) binding sites can be used to map putative
sites in uncharacterized promoter regions. SCPD provides
more up-to-date information specific to yeast than other
databases such as TRANSFAC (Wingender et al., 1996),
TRRD (Heinemeyer et al., 1998), EPD (Cavin Perier et al.,
1998) and TFD (Ghosh, 1998). All sequences in SCPD refer
to the corresponding genomic records in SGD (Cherry et al.,
1998) and GENBANK (Benson et al., 1998). Since for most
yeast genes the transcriptional start site (TSS) is not mapped,
the location of a DNA element in the promoter region is de-
fined relative to the translational start site (A of ATG is at +1).
SCPD incorporates differences in results of DNA footprint-
ing studies, terminologies (such as alternative gene names)
and reference sources. Mechanisms are also provided for
submitting data directly into SCPD by users.
To date, SCPD contains the information on ∼6223 open
reading frames and 2921 experimentally characterized
genes. It contains >1000 site records. Table 1 compares some
of the SCPD primary data with the yeast-related portion of
TRANSFAC (Release 3.4).
Table 1. Comparison between SCPD and TRANSFAC (Release 3.4)
Sites 312 (include artificial
Factors 159 (include those
with no mapped sites)
(with at least one
CoordinatesAs publishedFirst base of coding
region at +1
SequenceAs publishedReferred to SGD
???? ?? ??? ??? ????
? Oxford University Press 1999
J.Zhu and M.Q.Zhang
Fig. 1. Design of SCPD. (a) The ER model of SCPD. Box, entity; diamond, relationship; single oval, single value attribute; double oval,
multi-value attribute. Entities and relationships are connected by lines. Double lines denote a dependent relationship. (b) The object model of
SCPD. Classes are denoted by boxes. For each class, the first compartment denotes the name of the class, the second compartment contains the
variables and the third compartment contains methods.
Conceptual design of SCPD
SCPD was created in two phases. The first was to build an
entity-relationship (ER) model, which was used to explain
the storage of the promoter data. The second was to construct
an object model, which describes the dynamic features.
The ER model of SCPD is given in Figure 1a. It contains
the following entities: gene, factor, matrix, consensus, affin-
ity and putative_site, which are shown in boxes in Figure 1a.
The ovals linked to entities represent attributes. Double ovals
denote multivalue attributes. For example, the name attribute
of entity gene can have many alternative names.
In entity gene, intergenic_region defines the upstream re-
gion of a gene up to the boundary of its neighboring gene or
ORF. There are two types of intergenic regions. One consists
of the 5 regions of two genes, which are expected to be trans-
criptionally co-regulated. The other type consists of the 3 re-
gion of one gene and the 5 region of the other. In this case,
only one gene is expected to be transcriptional regulated.
However the transcriptional termination signals of the other
gene may exist as well. Promoter_region contains a graphi-
cal view of a promoter region in which the binding sites are
A promoter database of Saccharomyces cerevisiae
Figure 1. Continued
In SCPD, there is no distinction between the name of a
transcription factor and the name of its binding site. In entity
factor, coordinate is composed of three sub-attributes: start,
end and orientation. By default, the orientation is the forward
strand. A ‘c’ in orientation indicates the complementary
There are seven relationships defined in SCPD, denoted by
diamonds. Correlate represents the correlation between fac-
J.Zhu and M.Q.Zhang
Fig. 2. Distribution of transcription start sites. The start of the
translational start site is at 0. Most transcription start sites locate
50–100 bases upstream of the coding region. The median location
is –61, while the mean is –89.
tors. The correlation between factors is described by the con-
currence frequency, which is defined as the number of genes
having both factors’ sites over the total number of genes hav-
ing at least one factor’s site. Predicted_by is a ternary rela-
tionship among putative_site, matrix and consensus_pattern.
A putative site may be predicted by either a matrix or a con-
sensus_pattern. Matrices and consensi are derived from the
alignment of available mapped sites of individual factors.
The consensus patterns are determined using similar ap-
proach described in Fondrat and Kalogeropoulos (1996).
Other relationships are obvious in Figure 1a.
The ER model explains the storage of SCPD data. The
entries of SCPD are organized either in plain text files or in
a relational database operated by mSQL (Jepson and
Hughes, 1998). However, the ER model is inadequate to de-
scribe the dynamic features of SCPD. Figure 1b shows the
object model of SCPD. There are a variety of classes in
SCPD. Boxes denote classes. The name of each class is
shown in the first compartment, variables in the second and
methods in the third. The lines between classes represent
relationships. The numbers above the lines define their cardi-
nalities. The object model maps well onto a WWW interface
in which the links represent for objects, buttons for method,
and input text field or area for parameters.
General features of yeast transcription factors’ bind-
ing sites and regulatory elements
SCPD enables us to study the general features of yeast tran-
scription factors’ binding sites.
Many factors have multiple binding sites in their upstream
regions. For the 200 genes (455 non-redundant sites) docum-
ented in SCPD, 203 sites are in single copy, 69 in two copies,
19 in three, 9 in four, 3 in five and 1 in six. Sites with a large
copy number (such as six) are very rare. The lengths of bind-
ing sites range from 5 to 30 bp. The majority (78%) are lo-
cated between 5 and 16 bases. This is the most likely range
for detecting other novel sites. It is also worth mentioning
Fig. 3. Distribution of TATA boxes from 18 genes. The start of
translation is at 0. The median location is –177, the mean is –125.
Fig. 4. Distribution of all mapped sites documented in SCPD. The
translational start is at 0.
that the length of a site may depend on the experimental
method used to map it.
To answer a question such as where to find TF sites, one
first needs to know where RNA transcription starts. SCPD
contains 425 entries of TSS mapped in 172 genes. On aver-
age, each gene has ∼2–3 mapped transcription start sites.
Among these start sites, 183 (43%) start from A, 78 (18%)
from C, 71 (17%) from G and 93 (22%) from T. The consen-
sus sequence of TSS is rather loose. Figure 2 shows the dis-
tribution of these mapped TSSs. The translational start site
is at 0. The median TSS location is ∼61 bp upstream of the
translational start site, with the mean at 89 bp. Secondly, one
may want to know where the binding site for the pre-initi-
ation complex (PIC) is (see, for example, Roeder, 1996).
Since TBP (TATA box binding protein) is a part of the PIC,
the TATA box should be a good indicator of the PIC location.
Figure 3 shows the distribution of 22 known TBP binding
sites in the upstream regions of 18 genes. The median TATA
box position is 177 bp, and the mean at 125 bp upstream of
the translational start site. The distance between TSS and
TATA box is defined as the number of base pairs between the
first base of TATA box and the TSS. For this distance calcula-
tion, we used information on 12 genes (HIS4, UGA4, SUC2,
CYC1, CTS1, HSC82, ADH2, ARG1, ARG8, HIS3, CLN2
and GAL80). All of these genes have only one mapped
TATA box. We did not include the information on the GCY1
gene, which has two TATA boxes and five TSS. The average
A promoter database of Saccharomyces cerevisiae
Fig. 5. Main page of SCPD.
distance is 62 ± 30 bp. This is consistent with the observation
that the distance between yeast TATA element and mRNA
initiation site ranges between 40 and 120 bp (Struhl, 1987).
In contrast, for vertebrate promoters, the distance between
the TATA box and the TSS is only ∼25–30 bp (Bucher, 1990).
Figure 4 summarizes the distribution of all experimentally
mapped sites (not including TSS) documented in SCPD. The
majority were found in a range from 10 to 700 bp upstream
of the translational start site.
Figure 5 shows the screen shot of SCPD home page. A
number of simple but useful analysis tools are provided (see
on-line documentation for their usage). They may help users
to retrieve promoter sequences, identify known motifs and
predict putative sites. Tools like K-tuple relative information
and Gibbs sampler can be used to find new promoter el-
ements in the co-regulated gene cluster analysis of large-
scale gene expression experiments [examples may be found
in Zhang (1999)].
The authors would like to thank Dr J.Tabaska for reading the
manuscript and anonymous referees for critical suggestions.
This work was supported by Public Health Service grant
HG01696 from NIH/NIHGR (to M.Q.Z.).
Benson,D.A., Boguski,M.S., Lipman,D.J., Ostell,J. and Ouel-
lette,B.F.F. (1998) GenBank. Nucleic Acids Res., 26, 1–7.
Bucher,P. (1990) Weight matrix descriptions of four eukaryotic RNA II
promoter elements derived from 502 unrelated promoter sequences.
J. Mol. Biol., 212, 563–578.
Cavin Perier,R., Junier,T. and Bucher,P. (1998) The Eukaryotic
Promoter Database EPD. Nucleic Acids Res., 26, 353–357.
Cherry,M. et al. (1998) SGD: Saccharomyces Genome Database.
Nucleic Acids Res., 26, 73–79. http://genome-www.stanford.edu/
DeRisi,J.L., Iyer,V.R. and Brown,P.O. (1997) Exploring the metabolic
and genetic control of gene expression on a genomic scale. Science,
Fondrat,C. and Kalogeropoulos,A. (1996) Approaching the function
of new genes by detection of their potential upstream activation
sequences in Saccharomyces cerevisiae: application to chromosome
III. Comput. Appl. Biosci., 12, 363–374.
Ghosh,D. (1998) OOTFD (Object-Oriented Transcription Factors
Database): an object-oriented successor to TFD. Nucleic Acids Res.,
Goffeau,A. et al. (1996) Life with 6000 genes. Science, 274, 546.
Hampsey,M. (1998) Molecular genetics of the RNA polymerase II
general transcriptional machinery. Microbiol. Mol. Biol. Rev., 62,
Heinemeyer,T. et al. (1998) Databases on transcriptional regulation:
TRANSFAC, TRRD and COMPEL. Nucleic Acids Res., 26,
Jepson,B. and Hughes,D. (1998) Official Guide to Mini SQL. John
Wiley & Sons, New York. The URL is http://www.Hughes.com.au/
Roeder,R.G. (1996) The role of general initiation factors in transcrip-
tion by RNA polymerase II. Trends Biochem. Sci., 21, 327–335.
Struhl,K. (1987) Promoter, activator proteins, and the mechanism of
transcriptional initiation in yeast. Cell, 49, 295–297.
Wingender,E., Dietze,P., Karas,H. and Knuppel,R. (1996) TRANS-
FAC: a database on transcription factors and their DNA binding
sites. Nucleic Acids Res., 24, 238–241.
Zhang,M.Q. (1999) Promoter analysis of co-regulated genes in the
yeast genome. Comput. Chem., in press.