Promoter (genetics)

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As a promoter , and promoter (originally double. Promoteur , instigators, initiator), in the genetics a nucleotide sequence on the DNA referred to the regulated expression of a gene allows. The promoter is an essential part of a gene. It is located at the 5 'end of the non-template strand of the gene and thus in front of the RNA -coding area in the direction of synthesis . The most important property of a promoter is the specific interaction with certain DNA-binding proteins , which mediate the start of transcription of the gene by the RNA polymerase and are known as transcription factors .

The promoter is part of the “(gene) regulatory areas”. They also include nucleotide sequences that are further away from the gene, which can nevertheless influence its expression. So have enhancer a promoting effect on the expression silencers reduce this. Up to 2007, around 775 different promoters were known in the human genome . Thanks to the ENCODE research project, around 80,000 promoters, which make up 1.44% of the genome, were mapped in 2015. In addition there are about 130,000 dyadic (two-part) elements (0.99% of the genome), which were characterized either as enhancers , promoters, or as enhancers and promoters in the 111 epigenomes examined .

Bacterial promoters have a relatively uniform structure; here there are rather limited differences in the exact nucleotide sequence. Depending on the sequence, one speaks here of strong or weak promoters. The strength of a promoter can be predicted by comparing it with a consensus sequence from different promoters.

Eukaryotic promoters , on the other hand, are characterized by strong differences from one another. There are some widespread elements like the downstream promoter element , but a general eukaryotic promoter-specific nucleotide sequence is difficult to characterize. It is therefore not easy to record them using bioinformatic methods, for example in gene prediction . Therefore, promoters are now mainly mapped using high-throughput methods . The integrative analysis of RNA-Seq data, DNA accessibility for DNAsen, histone modification and DNA methylation allow the cell or tissue-specific identification of promoters in entire genomes.

General promoter elements

Sequence motifs that frequently occur in the promoters of a genome are referred to as general promoter elements , in contrast to specific promoter elements , which are only important for regulating the expression of a particular gene. The general transcription factors each bind specifically to the general promoter elements. These are either necessary for the initiation of DNA transcription or represent certain basic gene regulation mechanisms.

The TATA box of archaea and eukaryotes or the Pribnow box of bacteria are examples of a promoter element that occurs in a similar form in almost all organisms.

The part of a promoter which contains only those general promoter elements which are absolutely necessary for the transcription is the minimal or core promoter .

Often promoter elements are identified by their distance from the transcription start point , which is given the designation +1, while areas further “upstream” receive a negative sign, while areas further “downstream” retain their positive sign and the designation ± 0 (zero) is omitted remains.

Bacterial promoters

The most important general transcription factors in bacteria are the sigma factors . The structure of a promoter is therefore primarily dependent on which of the sigma factors it is recognized by. The conditions in the bacterial model organism Escherichia coli have been best investigated . By far the greatest number of promoters in E. coli are recognized by the factor Sigma-70.

Sigma-70 promoter

Using consensus sequences , the following general promoter elements can be classified in genes that have been transcribed with the help of the Sigma-70 factor:

  • the AT -basenpaarreiche UP element (for engl. upstream , upstream) above the -35 region ,
  • the −35 region , with the consensus sequence: 5'-TTGACA-3 ' ,
  • the −10 region , also known as the Pribnow box , with the consensus sequence: 5'-TATAAT-3 ' .

In the meantime, there is also evidence that the spacer sequences between the -35 and -10 regions are recognized by sigma-70 factors and that these thus influence the promoter activity.

It is also true that strong promoters are rich in AT base pairs directly before the starting point of transcription . This facilitates the unwinding of the double helix , which is necessary for transcription , since AT base pairs form fewer hydrogen bonds than GC base pairs.

The consensus sequences only give an approximate guide to the structure of a promoter. A particular Sigma-70 dependent promoter can deviate from these sequences in several places.

While the −35 region and Pribnow box are mainly recognized by the sigma factor, the UP element can interact directly with the α subunit of the bacterial RNA polymerase.

Promoters in archaea

Archaea , like bacteria, only have one RNA polymerase, which is homologous to eukaryotic RNA polymerase II. Therefore, the promoter sequences of archaea resemble those of eukaryotic RNA polymerase II promoters. However, the structure of the promoter itself is comparatively less complex in archaea.

Eukaryotic promoters

See the main article Eukaryotic Promoter .

Eukaryotes have four RNA polymerases, namely RNA polymerase I, II, III and IV. RNA polymerase I generates rRNA (ribosomal RNA), RNA polymerase II generates mRNA and snRNA (small nuclear RNA), RNA polymerase III generates tRNA , snRNA as well as 5S-rRNA and RNA polymerase IV generate siRNA (small interfering RNA). Each RNA polymerase in turn interacts with different transcription factors: It recognizes the transcription factor binding sites specific for the respective polymerase, the promoter area itself and the URS (upstream regulatory sequences). Furthermore, the number of general transcription factors in eukaryotes is significantly greater than in bacteria. Accordingly, initiation complexes of their own can form on the promoter, which can have a positive or negative effect on transcription. This is the reason for the variety of promoter sequences that can be recognized by a specific RNA polymerase in interaction with the respective transcription factors.

Individual evidence

  1. ↑ Campbell Biology 10th, updated edition; Reece et al .; Fig.17.8
  2. ↑ Elizabeth Pennisi: DNA Study Forces Rethink of What It Means to Be a Gene. In: Science . Vol. 316, 2007, pp. 1556-1557, PMID 17569836 doi : 10.1126 / science.316.5831.1556 .
  3. ↑ a b A. Kundaje, W. Meuleman, J. Ernst, M. Bilenky, A. Yen, A. Heravi-Moussavi, P. Kheradpour, Z. Zhang, J. Wang, MJ Ziller, V. Amin, JW Whitaker , MD Schultz, LD Ward, A. Sarkar, G. Quon, RS Sandstrom, ML Eaton, YC Wu, AR Pfenning, X. Wang, M. Claussnitzer, Y. Liu, C. Coarfa, RA Harris, N. Shoresh, CB Epstein, E. Gjoneska, D. Leung, W. Xie, RD Hawkins, R. Lister, C. Hong, P. Gascard, AJ Mungall, R. Moore, E. Chuah, A. Tam, TK Canfield, RS Hansen , R. Kaul, PJ Sabo, MS Bansal, A. Carles, JR Dixon, KH Farh, S. Feizi, R. Karlic, AR Kim, A. Kulkarni, D. Li, R. Lowdon, G. Elliott, TR Mercer , SJ Neph, V. Onuchic, P. Polak, N. Rajagopal, P. Ray, RC Sallari, KT Siebenthall, NA Sinnott-Armstrong, M. Stevens, RE Thurman, J. Wu, B. Zhang, X. Zhou, AE Beaudet, LA Boyer, PL De Jager, PJ Farnham, SJ Fisher, D. Haussler, SJ Jones, W. Li, MA Marra, MT McManus, S. Sunyaev, JA Thomson, TD Tlsty, LH Tsai, W. Wang, RA Waterland, MQ Zhang, LH Chadwick, BE Bernstein, JF Costello, JR Ecker, M. Hirst, A. Meis sner, A. Milosavljevic, B. Ren, JA Stamatoyannopoulos, T. Wang, M. Kellis: Integrative analysis of 111 reference human epigenomes. In: Nature. Volume 518, number 7539, February 2015, pp. 317-330, doi : 10.1038 / nature14248 , PMID 25693563 , PMC 4530010 (free full text).
  4. ↑ MS Paget: Bacterial Sigma Factors and Anti-Sigma Factors: Structure, Function and Distribution. In: Biomolecules. Volume 5, number 3, June 2015, pp. 1245-1265, doi : 10.3390 / biom5031245 , PMID 26131973 , PMC 4598750 (free full text) (review).
  5. ↑ Shivani S. Singh, Athanasios Typas, Regine Hengge , David C. Grainger: Escherichia coli σ70 senses sequence and conformation of the promoter spacer region. In: Nucleic Acids Research . Vol. 39, 2011, ISSN  0305-1048 , pp. 5109-5118.
  6. ↑ A. Hirata, KS Murakami: Archaeal RNA polymerase. In: Current opinion in structural biology. Volume 19, number 6, December 2009, pp. 724-731, doi : 10.1016 / j.sbi.2009.10.006 , PMID 19880312 , PMC 2806685 (free full text) (review).

literature

  • Rolf Knippers: Molecular Genetics. 8th, revised edition. Georg Thieme Verlag, New York NY et al. 2001, ISBN 3-13-477008-3 .

See also