Editing Promoter (genetics) (section)

=== Bacterial ===
In [[bacteria]], the promoter contains two short sequence elements approximately 10 ([[Pribnow box|Pribnow Box]]) and 35 nucleotides ''upstream'' from the [[transcription start site]].<ref name=":0" />
* The sequence at -10 (the -10 element) has the [[consensus sequence]] TATAAT.
* The sequence at -35 (the -35 element) has the consensus sequence TTGACA.
* The above consensus sequences, while conserved on average, are not found intact in most promoters. On average, only 3 to 4 of the 6 base pairs in each consensus sequence are found in any given promoter. Few natural promoters have been identified to date that possess intact consensus sequences at both the -10 and -35; artificial promoters with complete conservation of the -10 and -35 elements have been found to transcribe at lower frequencies than those with a few mismatches with the consensus.
* The optimal spacing between the -35 and -10 sequences is 17 bp. The spacer sequence affects promoter strength by up to 600-fold.<ref name=kuo25/>
* Some promoters contain one or more upstream promoter element (UP element) subsites<ref name="Ross 1998">{{cite journal | vauthors = Ross W, Gosink KK, Salomon J, Igarashi K, Zou C, Ishihama A, Severinov K, Gourse RL | display-authors = 6 | title = A third recognition element in bacterial promoters: DNA binding by the alpha subunit of RNA polymerase | journal = Science | volume = 262 | issue = 5138 | pages = 1407–1413 | date = November 1993 | pmid = 8248780 | doi = 10.1126/science.8248780 | bibcode = 1993Sci...262.1407R }}</ref> ([[consensus sequence]] 5'-AAAAAARNR-3' when centered in the -42 region; consensus sequence 5'-AWWWWWTTTTT-3' when centered in the -52 region; W = A or T; R = A or G; N = any base).<ref>{{cite journal | vauthors = Estrem ST, Ross W, Gaal T, Chen ZW, Niu W, Ebright RH, Gourse RL | title = Bacterial promoter architecture: subsite structure of UP elements and interactions with the carboxy-terminal domain of the RNA polymerase alpha subunit | journal = Genes & Development | volume = 13 | issue = 16 | pages = 2134–2147 | date = August 1999 | pmid = 10465790 | pmc = 316962 | doi = 10.1101/gad.13.16.2134 }}</ref>
* The transcription start site has the consensus sequence YRY.<ref name=kuo25>{{Cite journal| doi = 10.1101/2025.01.23.634641| pages = 2025–01.23.634641| last1 = Kuo| first1 = Syue-Ting| last2 = Chang| first2 = Joshua Kevin| last3 = Chang| first3 = Clara| last4 = Shen| first4 = Wei-Yi| last5 = Hsu| first5 = Christine| last6 = Lai| first6 = Sheng-Wen| last7 = Chou| first7 = Hsin-Hung David| title = Unravel the start element and promoter architecture across the domain Bacteria| journal = bioRxiv| date = 2025-01-01}}</ref>

The above promoter sequences are recognized only by RNA polymerase [[holoenzyme]] containing [[sigma-70]]. RNA polymerase holoenzymes containing other sigma factors recognize different core promoter sequences.

 ← upstream                                                                     downstream →
 5'-XXXXXXXPPPPPPXXXXXXPPPPPPXXXXGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGGXXXX-3'
            -35       -10       Gene to be transcribed

====Probability of occurrence of each nucleotide====
  for -10 sequence
  T    A    T    A    A   T
 77%  76%  60%  61%  56%  82%

  for -35 sequence
  T    T    G    A    C    A
 69%  79%  61%  56%  54%  54%

==== Bidirectional (prokaryotic) ====
Promoters can be very closely located in the DNA. Such "closely spaced promoters" have been observed in the DNAs of all life forms, from humans<ref name="Adachi_2002">{{cite journal | vauthors = Adachi N, Lieber MR | title = Bidirectional gene organization: a common architectural feature of the human genome | journal = Cell | volume = 109 | issue = 7 | pages = 807–809 | date = June 2002 | pmid = 12110178 | doi = 10.1016/S0092-8674(02)00758-4 | doi-access = free }}</ref> to prokaryotes<ref name=" Herbert_1986">{{cite journal | vauthors = Herbert M, Kolb A, Buc H | title = Overlapping promoters and their control in Escherichia coli: the gal case | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 83 | issue = 9 | pages = 2807–2811 | date = May 1986 | pmid = 3010319 | pmc = 323395 | doi = 10.1073/pnas.83.9.2807 | doi-access = free | bibcode = 1986PNAS...83.2807H }}</ref> and are highly conserved.<ref name=" Korbel_2004">{{cite journal | vauthors = Korbel JO, Jensen LJ, von Mering C, Bork P | title = Analysis of genomic context: prediction of functional associations from conserved bidirectionally transcribed gene pairs | journal = Nature Biotechnology | volume = 22 | issue = 7 | pages = 911–917 | date = July 2004 | pmid = 15229555 | doi = 10.1038/nbt988 | s2cid = 3546895 | doi-access =  }}</ref> Therefore, they may provide some (presently unknown) advantages.
These pairs of promoters can be positioned in divergent, tandem, and convergent directions. They can also be regulated by transcription factors and differ in various features, such as the nucleotide distance between them, the two promoter strengths, etc.
The most important aspect of two closely spaced promoters is that they will, most likely, interfere with each other. Several studies have explored this using both analytical and stochastic models.<ref name=" Sneppen_2005">{{cite journal | vauthors = Sneppen K, Dodd IB, Shearwin KE, Palmer AC, Schubert RA, Callen BP, Egan JB | title = A mathematical model for transcriptional interference by RNA polymerase traffic in Escherichia coli | journal = Journal of Molecular Biology | volume = 346 | issue = 2 | pages = 399–409 | date = February 2005 | pmid = 15670592 | doi = 10.1016/j.jmb.2004.11.075 | doi-access =  }}</ref><ref name=" Martins_2012">{{cite journal | vauthors = Martins L, Mäkelä J, Häkkinen A, Kandhavelu M, Yli-Harja O, Fonseca JM, Ribeiro AS | title = Dynamics of transcription of closely spaced promoters in Escherichia coli, one event at a time | journal = Journal of Theoretical Biology | volume = 301 | pages = 83–94 | date = May 2012 | pmid = 22370562 | doi = 10.1016/j.jtbi.2012.02.015 | doi-access =  | bibcode = 2012JThBi.301...83M }}</ref><ref name="Hakkinen_2016">{{cite journal | vauthors = Häkkinen A, Oliveira SM, Neeli-Venkata R, Ribeiro AS | title = Transcription closed and open complex formation coordinate expression of genes with a shared promoter region | journal = Journal of the Royal Society, Interface | volume = 16 | issue = 161 | pages = 20190507 | date = December 2019 | pmid = 31822223 | pmc = 6936044 | doi = 10.1098/rsif.2019.0507 | doi-access = free }}</ref> There are also studies that measured gene expression in synthetic genes or from one to a few genes controlled by bidirectional promoters.<ref name=" Bordoy_2016">{{cite journal | vauthors = Bordoy AE, Varanasi US, Courtney CM, Chatterjee A | title = Transcriptional Interference in Convergent Promoters as a Means for Tunable Gene Expression | journal = ACS Synthetic Biology | volume = 5 | issue = 12 | pages = 1331–1341 | date = December 2016 | pmid = 27346626 | doi = 10.1021/acssynbio.5b00223 | doi-access =  }}</ref>

[[File:These are two tandem promoters with occlusion – March 2022 TP686.png|thumb|Depiction the phenomenon of interference between tandem promoters. Figure created with BioRender.com]]

More recently, one study measured most genes controlled by tandem promoters in ''E. coli''.<ref name=" Chauhan_2022">{{cite journal | vauthors = Chauhan V, Bahrudeen MN, Palma CS, Baptista IS, Almeida BL, Dash S, Kandavalli V, Ribeiro AS | display-authors = 6 | title = Analytical kinetic model of native tandem promoters in E. coli | journal = PLOS Computational Biology | volume = 18 | issue = 1 | pages = e1009824 | date = January 2022 | pmid = 35100257 | pmc = 8830795 | doi = 10.1371/journal.pcbi.1009824 | doi-access = free | bibcode = 2022PLSCB..18E9824C }}</ref> In that study, two main forms of interference were measured. One is when an RNAP is on the downstream promoter, blocking the movement of RNAPs elongating from the upstream promoter. The other is when the two promoters are so close that when an RNAP sits on one of the promoters, it blocks any other RNAP from reaching the other promoter. These events are possible because the RNAP occupies several nucleotides when bound to the DNA, including in transcription start sites.
Similar events occur when the promoters are in divergent and convergent formations. The possible events also depend on the distance between them.