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Gene transcriptions/Promoters

The diagram shows the RNA polymerase II holoenzyme attached to the DNA template strand. Credit: ArneLH.

Although human DNA like most other life forms on Earth has two strands forming a double helix, only one of the strands, the template strand, is usually used to transcribe a gene product such as messenger ribonucleic acid (mRNA).

On the template strand is a nucleotide sequence (the gene promoter) that is usually interacted with by the transcription mechanism before any product of the gene is transcribed.

GeneticsEdit

Eukaryotic promoters are extremely diverse and are difficult to characterize. They typically lie upstream of the gene and can have regulatory elements several kilobases away from the transcriptional start site (enhancers). In eukaryotes, the transcriptional complex can cause the DNA to bend back on itself, which allows for placement of regulatory sequences far from the actual site of transcription.

GenesEdit

Def. a "unit of heredity; a segment of DNA or RNA that is transmitted from one generation to the next, and that carries genetic information such as the sequence of amino acids for a protein"[1] is called a gene.

EukaryotesEdit

Def. any "of the single-celled or multicellular organisms, of the taxonomic domain Eukaryota, whose cells contain at least one distinct nucleus"[2] is called a eukaryote.

Def. a "domain - all organisms whose cells have a nucleus"[3] is called Eukaryota.

PositionsEdit

Positions of nucleotides in the promoter are designated relative to the transcription start site (TSS).

Positions upstream from the TSS are negative numbers counting back from -1, for example, -100 is a position 100 nucleotides upstream from the TSS.

Theoretical gene promotersEdit

Def. the "section of DNA that controls the initiation of RNA transcription as a product of a gene"[4] is called a gene promoter, or a promoter in the field of genetics.

OperonsEdit

Def. a "unit of genetic material that functions in a coordinated manner by means of an operator, a promoter, and structural genes that are transcribed together"[5] is called an operon.

StimulonsEdit

Def. a "system of genes that are regulated by the same stimulus"[6] is called a stimulon.

RegulonsEdit

Def. a "group of genes that is regulated by the same regulatory molecule"[7] is called a regulon.

"The genes of a regulon share a common regulatory element binding site or promoter. The genes comprising a regulon may be located non-contiguously in the genome."[7]

Proximal promotersEdit

Def. any proximal nucleotide sequence upstream of the gene that tends to contain primary regulatory elements is called a proximal promoter.

Core promotersEdit

The core promoter is the minimal portion of the promoter required to properly initiate gene transcription.[8] It contains a binding site for RNA polymerase (RNA polymerase I, RNA polymerase II, or RNA polymerase III).

A vast network of regulatory factors that contribute to the initiation of transcription by RNA polymerase ultimately target any specific gene’s core promoter.

The core promoter includes the transcription start site(s) (TSS).

That portion of the core promoter that is upstream of the TSS is also part of the proximal promoter.

Dispersed promotersEdit

A dispersed promoter is a region of DNA that facilitates the transcription of a particular gene, where this promoter region contains several transcription start sites over 50-100 nucleotides.

Dispersed promoters are more recent and less widespread throughout nature than focused promoters.[9]

Focused promotersEdit

A focused promoter contains either a single transcription start site or a distinct cluster of start sites over several nucleotides.[9] Focused promoters are sometimes referred to as narrow peak (NP) promoters.[10]

Distal promotersEdit

Def. any distal nucleotide sequence upstream of the gene that may contain additional regulatory elements, often with a weaker influence than any sequence within the proximal promoter, is called a distal promoter.

Distal promoter regions may be a relatively small number of nucleotides, fairly close to the TSS such as (-253 to -54)[11] or several regions of different lengths, many nucleotides away, such as (-2732 to -2600) and (-2830 to -2800).[12]

The "[d]istal promoter is not a spacer element."[13]

Expression of a specific gene such as that for aromatase may vary with tissue type: "expression in ovary utilizes a proximal promoter that is regulated primarily by cAMP. On the other hand, expression in placenta utilizes a distal promoter that is located at least 40 kb upstream of the start of transcription and that is regulated by retinoids."[14]

Downstream promotersEdit

"[N]onredundant human promoter sequences 600 bp long (−499 to +100 bp around the TSS) [are available] from [the] Eukaryotic Promoter Database (EPD) release 75 (4, 68) (http://www.epd.isb-sib.ch/), and ... promoters sequences 1,200 bp long (−1,000 to +200 bp) [are available] from the Database of Transcriptional Start Sites (DBTSS) (59, 74, 75) (http://dbtss.hgc.jp/index.html)"[15].

Downstream core elementsEdit

The downstream core element (DCE) is a transcription core promoter sequence that is within the transcribed portion of a gene.

The consensus sequence for the DCE is CTTC...CTGT...AGC.[15] These three consensus elements are referred to as subelements: "SI is CTTC, SII is CTGT, and SIII is AGC."[15]

The number of nucleotides between each subelement can apparently vary down to none.

A core promoter that contains all three subelements may be much less common than one containing only one or two.[15] "SI resides approximately from +6 to +11, SII from +16 to +21, and SIII from +30 to +34."[15]

SI as 3'-CTTC-5' can occur as 3 of 4 (CTT, TTC) or 4 of 4 (CTTC). SII as 3'-CTGT-5' can also occur as 3 of 4 (CTG, TGT) or 4 of 4 (CTGT). SIII as AGC is not known to vary.

DCE SIII can function independently of SI and SII.[15]

Transcription factor II D (TFIID), a transcription factor that is part of the RNA polymerase II holoenzyme, interacts with promoters containing only SIII of the DCE suggesting a critical spacing parameter between SIII and the TATA box, initiator element, or some combination of the two.[15] TFIID probably serves as a core promoter recognition complex.[15]

TAF1 interacts with the DCE in a sequence-dependent manner.[15]

The differences between core promoters with downstream elements may be explained by

  1. "TATA- and DPE-dependent promoters are specific for particular enhancers"[15],
  2. "preferences of activators for specific core promoter architectures"[15], and
  3. "the presence of a DCE or [downstream core promoter element (DPE)] might be indicative of an architecture designed for specific regulatory networks, such as the regulation of housekeeping promoters versus tissue-specific promoters (or other highly regulated promoters) or the regulation of subsets of viral promoters."[15]

Motif ten elementsEdit

The motif ten element (MTE) is a downstream core promoter element that "promotes transcription by RNA polymerase II when it is located precisely at positions +18 to +27 relative to A+1 in the initiator (Inr) element."[16]

The motif 10 consensus sequence is CSARCSSAACGS [5'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-3'].[16] By convention, the consensus sequence 5'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-3' is stated as it would be translated into mRNA. In the direction of transcription on the template strand this consensus sequence becomes 3'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-5'.

Downstream promoter elementsEdit

The downstream promoter element (DPE) is a core promoter element present in other species including humans and excluding Saccharomyces cerevisiae.[17] Like all core promoters, the DPE plays an important role in the initiation of gene transcription by RNA polymerase II.

The core sequence of the DPE is located precisely +28 to +32 nts relative to the A+1 nt in the Inr.[18]

HypothesesEdit

  1. Promoters include those that are downstream and those that are upstream.

See alsoEdit

ReferencesEdit

  1. gene. San Francisco, California: Wikimedia Foundation, Inc. December 13, 2012. Retrieved 2012-12-13.
  2. eukaryote. San Francisco, California: Wikimedia Foundation, Inc. August 28, 2012. Retrieved 2012-09-29.
  3. Eukaryota. San Francisco, California: Wikimedia Foundation, Inc. December 26, 2012. Retrieved 2012-09-29.
  4. promoter. San Francisco, California: Wikimedia Foundation, Inc. September 20, 2012. Retrieved 2012-09-29.
  5. operon. San Francisco, California: Wikimedia Foundation, Inc. November 19, 2012. Retrieved 2012-12-13.
  6. stimulon. San Francisco, California: Wikimedia Foundation, Inc. August 13, 2012. Retrieved 2012-12-13.
  7. 7.0 7.1 regulon. San Francisco, California: Wikimedia Foundation, Inc. November 29, 2012. Retrieved 2012-12-13.
  8. Stephen T. Smale and James T. Kadonaga (July 2003). "The RNA Polymerase II Core Promoter". Annual Review of Biochemistry 72 (1): 449-79. doi:10.1146/annurev.biochem.72.121801.161520. PMID 12651739. http://www.annualreviews.org/doi/abs/10.1146/annurev.biochem.72.121801.161520. Retrieved 2012-05-07. 
  9. 9.0 9.1 T Juven-Gershon, JY Hsu, JWM Theisen, JT Kadonaga (June 2008). "The RNA polymerase II core promoter - the gateway to transcription". Current Opinion in Cell Biology 20 (3): 253-9. doi:10.1016/j.ceb.2008.03.003. PMID 18436437. 
  10. Rach EA, Winter DR, Benjamin AM, Corcoran DL, Ni T, Zhu J, Ohler U (January 2011). "Transcription initiation patterns indicate divergent strategies for gene regulation at the chromatin level". PLoS Genetics 7 (1): e1001274. doi:10.1371/journal.pgen.1001274. PMID 21249180. 
  11. A Aoyama, T Tamura, K Mikoshiba (March 1990). "Regulation of brain-specific transcription of the mouse myelin basic protein gene: function of the NFI-binding site in the distal promoter". Biochemical and Biophysical Research Communications 167 (2): 648-53. doi:10.1016/0006-291X(90)92074-A. http://www.sciencedirect.com/science/article/pii/0006291X9092074A. Retrieved 2012-12-13. 
  12. J Gao and L Tseng (June 1996). "Distal Sp3 binding sites in the hIGBP-1 gene promoter suppress transcriptional repression in decidualized human endometrial stromal cells: identification of a novel Sp3 form in decidual cells". Molecular Endocrinology 10 (6): 613-21. doi:10.1210/me.10.6.613. http://mend.endojournals.org/content/10/6/613.short. Retrieved 2012-12-13. 
  13. Peter Pasceri, Dylan Pannell, Xiumei Wu, and James Ellis (July 15, 1998). "Full activity from human β-globin locus control region transgenes requires 5′ HS1, distal β-globin promoter, and 3′ β-globin sequences". Blood 92 (2): 653-63. http://bloodjournal.hematologylibrary.org/content/92/2/653.short. Retrieved 2012-12-13. 
  14. ER Simpson, Y Zhao, VR Agarwal, MD Michael, SE Bulun, MM Hinschelwood, S Graham-Lorence, T Sun, CR Fisher, K Qin, CR Mendelson (1997). "Aromatase expression in health and disease". Recent Progress in Hormone Research 52: 185-213. PMID 9238853. http://europepmc.org/abstract/MED/9238853/reload=0;jsessionid=ZkDZMTISuVyyp1BDa6GR.10. Retrieved 2012-12-13. 
  15. 15.00 15.01 15.02 15.03 15.04 15.05 15.06 15.07 15.08 15.09 15.10 15.11 Dong-Hoon Lee, Naum Gershenzon, Malavika Gupta, Ilya P. Ioshikhes, Danny Reinberg and Brian A. Lewis (November 2005). "Functional Characterization of Core Promoter Elements: the Downstream Core Element Is Recognized by TAF1". Molecular and Cellular Biology 25 (21): 9674-86. doi:10.1128/MCB.25.21.9674-9686.2005. PMID 16227614. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1265815/. Retrieved 2010-10-23. 
  16. 16.0 16.1 Chin Yan Lim, Buyung Santoso, Thomas Boulay, Emily Dong, Uwe Ohler, and James T. Kadonaga (July 1, 2004). "The MTE, a new core promoter element for transcription by RNA polymerase II". Genes & Development 18 (13): 1606-17. doi:10.1101/gad.1193404. PMID 15231738. http://genesdev.cshlp.org/content/18/13/1606.full. Retrieved 2013-02-10. 
  17. Tamar Juven-Gershon, James T. Kadonaga (March 15, 2010). "Regulation of Gene Expression via the Core Promoter and the Basal Transcriptional Machinery". Developmental Biology 339 (2): 225–9. doi:10.1016/j.ydbio.2009.08.009. PMID 19682982. PMC 2830304. //www.ncbi.nlm.nih.gov/pmc/articles/PMC2830304/. 
  18. Alan K. Kutach, James T. Kadonaga (July 2000). "The Downstream Promoter Element DPE Appears To Be as Widely Used as the TATA Box in Drosophila Core Promoters". Molecular and Cellular Biology 20 (13): 4754-64. PMID 10848601. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC85905/. Retrieved 2012-07-15. 

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