Kel O.V.1, Kel A.E.1,2, Romashchenko A.G.1, Wingender E.2, Kolchanov N.A.1
1Institute of Cytology and Genetics SB RAS, 630090, Novosibirsk, pr. Lavrentyeva-10, Russia;
2Gesellschaft fuer Biotechnologische Forschung mbH, Mascheroder Weg 1, D-38124 Braunschweig, Germany; E-mail: okel@bionet.nsc.ru; FAX: 049(531)6181 266.
The COMPEL database was developed to compile information about composite elements (CEs) revealed in the regulatory regions of eukaryotic genes. The composite elements contain two closely situated binding sites for transcription factors that may differ in the structure of the DNA-binding and activation domains as well as in functional properties (tissue-specificity, inducibility by extracellular signals, among others). Interaction between two factors within a CE may provide a new combinatorial feature of transcriptional regulation.
Each entry of the database corresponds to a CE and contains its sequence, location in the gene, transcription factors involved, experiments that were done to reveal CE, and functional features of the CE in gene transcription regulation. With regard to the functional interaction between the factors involved, CE are divided into two types: synergistic and antagonistic. Composite elements of synergistic type contain sites for transcription factors that simultaneously bind to DNA and synergistically activate transcription. For CEs of antagonistic type, two transcription factors influence transcription in opposite directions: the first functions as an activator and the other as a repressor. At present, COMPEL describes 146 composite elements in 79 different genes of vertebrates and their viruses. 118 of the composite elements belong to synergistic type and 28 to antagonistic type. In the present work we propose a classification of CEs based on gene expression pattern they are essential for. There are (i) CEs that confer cell-specific regulation including that in liver, T; B- and myeloid cells, muscle, pituitary (ii) CEs mediating induction by steroid hormones, interleukins, other molecular signals, gene inducibility during acute-phase and immune response; (iii) CEs regulating cell-cycle dependent gene expression; (iv) CEs involved in developmental control.
Being very specific transcription regulators, CEs are sensitive indicators of the regulatory function of the sequence under analysis. On the basis of the sequence and structural information stored in the COMPEL database we are creating a number of new methods for recognition of different CEs in genomic sequences (http://wwwmgs.bionet.nsc.ru/Programs/funsite/). COMPEL is accessible by (ftp://transfac.gbf.de/pub/databases/compel/).
This work was funded by the Russian and German Ministries of Sciences, by the Siberian Branch of Russian Academy of Sciences, as well as by the North Atlantic Treaty Organization (grant N 951149).