AG BIODV, Institute of Experimental Genetics, GSF-National Research Center
for Environment and Health,
Ingolstaedter Landstr. 1,
D-85764 Neuherberg
Phone: +89-3187-4050
Fax: +89-3187-4400
E-mail: werner@gsf.de
www:http://www.gsf.de/biodv
Genomatix Software GmbH,
Landsberger Str. 6,
D-80339 München
Phone: 089 599766-0
Fax: 089 599766-55
The annotation of human genomic sequences is far from complete and "anonymous" still describes a major part of the genomic sequences because experimental evaluation is unable to keep pace with sequencing. Therefore, rapid and precise functional annotation of the collected large-scale sequences by in silico methods will be mandatory. In order to understand biological functions of genes it will be especially important to elucidate also features that depend on the genomic context rather than being intrinsic to individual gene. For example, analysis of the amino acid sequences derived from a gene allows elucidation of intrinsic features of the protein. However, this should not be confused with the elucidation of the function(s) of the gene because a significant portion of the gene functions cannot be determined from the amino acid sequence. The trivial case is that the protein only has a partial function (e.g. as a part of a functional heterodimer). Unless the partner(s) are known there is no way to determine the function. Another less obvious reason is that the amino acid sequence only provides the information which protein can be encoded, but no clue to where and when this might be happening.
The central processor of gene regulation is the gene promoter, which by definition comprises the 5'-end of the transcribed sequence. There is a variety of other elements like matrix attachment (S/MAR) or locus control regions (LCR), enhancers, silencers influencing transcription. However, none of these other control regions can have any effect on the actual transcription of the gene unless its signals are integrated and executed within the promoter of the gene, as only there the RNA polymerase binds. Therefore, promoters can be seen as the central processing unit of gene transcription. Nevertheless, promoters tell relatively little about gene regulation if looked at in isolation. The actual behavior of a promoter is determined by the nature and quantities of transcription factors (specialized proteins) within the cell and cannot be determined solely from the promoter sequence. As in case of the amino acid sequence, the promoter sequence just determines, what kind of regulation is possible, not what is really happening in a given cell and situation.
A short survey will be given about how to find promoters in large genomic sequences followed by the reasoning of how to compare promoter sequences in order to elucidate the functional context of genes. Promoters can no longer be treated as functional units as the same promoter may have quite different functions in a different cellular context. This illustrates that there is no way to determine the promoter function in a single analysis as often promoters have not one but several different functions.