Nucleic Acids Research

Figure 1. Mood/ooTFD representation for yeast SAGA, as viewed through the experimental Java Applet interface. For sake of convenience, only two (yTAF90, yTAF60) are presented here. The remaining polypeptide components (GCN5, yTAF17, yTAF61, yTAF25, SPT3, ADA1, ADA2, ADA3, SPT7, SPT8, SPT20) are also present in the results of this query and are viewable by scrolling down the query results screen.

OoTFD (object oriented Transcription Factors Database) is a successor to rTFD (Relational Transcription Factors Database; 1), and is designed to focus on the composite object relationships in transcription factors and gene expression. The need for database representations for these types of relationships owes to the general current paradigm in this field, in which protein-protein interactions are considered to be as important, if not more so, than protein-DNA interactions. These types of interactions are an essential aspect of gene regulation in higher eukaryotes, but are found in prokaryotes as well. In the past year, there has been a small increase in the numbers of entries in the database, and a number of new tools to facilitate data access to this database and associated resources have been developed. The current database contents, in terms of numbers of entries per object class, are presented in Table 1. Two object database systems, ozone (a pure Java object database system) and Mood (Materials object-oriented database) have been used in the past year in developing this database. Objects in the latter representation of ooTFD can be accessed through the Mood experimental Java-applet based interface. A transcription factor representation accessible through this interface is presented (Fig. 1) for the multiprotein complex SAGA (Spt-Ada-Gcn acetyltransferase), the transcriptional coactivator in yeast which interacts with but does not contain TBP (TATA binding protein), and facilitates RNA polymerase transcription initiation by acetylation of nucleosome proteins (reviewed in refs 2 and 3). Computational representations for these and similar multiprotein complexes (TFTC, p300/CBP/PCAF, STAGA) which currently exist as ooTFD objects, and their relationship to the polII transcription machinery, may be of some usefulness in gaining an understanding of the biology of the interface between transcriptional regulation and other cellular events, as has been suggested for the p300/CBP complex in signal transduction (4). The IFTI-MIRAGE site contains, in addition to database and sequence analysis tools directly associated with ooTFD, ~75 links to gene regulation related web resources, including those of other databases related to transcriptional regulation (5-10).

A

B

Figure 2. TF-Advisor interface. (A) Views from an interactive session with TF-Advisor, in which a user is directed to an ozone predefined query to retrieve all ooTFD/Sites entries for sequences recognized by a transcription factor. The question in the right panel is the last in a series of questions that the user is asked. (B) Actual results of a query, involving all the known binding sites for a transcription factor, performed with HNF-4 (Hepatocyte Nuclear Factor 4).

Table 1.

Data structure	No. of entries
Factors	532
Polypeptides	2359
Sites	5611
Domains	1016
References	20 211
Names	1122
Ligands	18
siteProfiles	457
domainProfiles	15

DATA RETRIEVAL

Access to ooTFD is possible through database servers for either of the object database systems (ozone, Mood) described here. Although queries against this database resource through standard relational database query languages have been possible for some time, the current focus on query and retrieval capabilities for this resource is in the development of utilities for certain `predefined' or `canned' queries, in accordance with some of the commonly performed queries which are of interest to the community. In the interface to the ozone representation of ooTFD, these predefined queries include those such as `What known binding sites are recognized by transcription factor X?', `What is the polypeptide composition of transcription factor X?', and `What are all the transcription factors that contain polypeptide X?'. Another step in the interests of developing end-user access tools is TF-Advisor, an intelligent or `knowledge-based' web tool that directs a new user to the proper database or sequence analysis tool for a particular problem, through a series of questions. Figure 2 presents a typical output from a TF-Advisor interactive session. The transcription factor sequence analysis approaches currently available through this site include blastp/tfdaa, threedb/polypeptides, profilesearch/domainprofiles, pfscan/siteprofiles, and dynamicplus/sites (summarized in Table 2). In addition to access tools for ooTFD, 117 transcription factor PDB structures, organized and retrievable by DNA-binding domain family, are available through the IFTI-MIRAGE site, and can be viewed using Webmol, a Java-based PDB structure viewer (11). As the needs of the community in transcription factor information retrieval evolve, new functionalities will be added to the repertoire of predefined queries available to end-user biologists.

Table 2.

Sequence analysis approach	Sequence type	Description
blastp/tfdaa	amino acid	blastp analysis of a protein sequence against domains and polyeptides sequences
threedb/polypeptides	amino acid	three-way (fasta-like) analysis against polypeptides sequences
profilesearch/domainProfiles	amino acid	analysis of a protein sequence against DNA-binding domain profiles
Tfsitescan (dynamicplus/Sites)	nucleic acid	analysis of a promoter against sites sequences
Tfsitescan (pfscan/siteProfiles)	nucleic acid	analysis of a promoter against sites matrices

CITING THIS RESOURCE

Users are asked to cite this publication in reporting results derived by accesses to this database.

REFERENCES

1. Ghosh,D. (1990) Nucleic Acids Res., 18, 1749-1756. MEDLINE Abstract

2. Struhl,K. and Moqtaderi,Z. (1998) Cell, 94, 1-4. MEDLINE Abstract

3. Grant,P.A., Sterner,D.E., Duggan,L.J., Workman,J.L. and Berger,S.L. (1998) Trends Cell Biol., 8, 193-197. MEDLINE Abstract

4. Torchia,J, Rose,D.W., Inostroza,J., Kamei,Y., Westin,S., Glass,C.K. and Rosenfeld,M.G. (1997) Nature, 387, 677-684. MEDLINE Abstract

5. Huerta,A.M., Salgado,H., Thieffry,D. and Collado-Vides,J. (1998) Nucleic Acids Res., 26, 55-60. MEDLINE Abstract

6. Salas,F., Haas,J., Brunk,B., Stoeckert,C.J. and Overton,G.C. (1998) Nucleic Acids Res., 26, 288-289. MEDLINE Abstract

7. Perier,R.C., Junier,T., and Bucher,P. (1998) Nucleic Acids Res., 26, 353-357.

8. Higo,K., Ugawa,Y., Iwamoto,M. and Higo,H. (1998) Nucleic Acids Res., 26, 358-359. MEDLINE Abstract

9. Heinemeyer,T., Wingender,E., Reuter,I., Hermjakob,H., Kel,A.E., Kel,O.V., Ignatieva,E.V., Ananko,E.A., Podkolodnaya,O.A., Kolpakov,F.A., Podkolodny,N.L. and Kolchanov,N.A. (1998) Nucleic Acids Res., 26, 362-367. MEDLINE Abstract

10. Baxevanis,A.D. and Landsman,D. (1998) Nucleic Acids Res., 26, 272-275.

11. Walther,D. (1997) Trends Biochem. Sci., 22, 274-275. MEDLINE Abstract

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*Tel: +1 800 894 4770; Fax: +1 800 894 4770; Email: dghosh@ifti.org

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