Gene transcriptions/Elements/Downstream cores

< Gene transcriptions < Elements

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

Downstream

Def. "[l]ower down, in relation to a river or stream ... [f]ollowing the path of a river or stream"[1] is called downstream.

By analogy, gene transcription follows a path along the human DNA template strand once the RNA polymerase II holoenzyme locates the transcription start site (TSS).

Cores

Def. "[t]he central part ... heart ... center or inner part ... [t]he most important part of a thing ... [an] inside"[2] is called a core.

Consensus sequences

The consensus sequence for the DCE is CTTC...CTGT...AGC.[3] These three consensus elements are referred to as subelements: "SI is CTTC, SII is CTGT, and SIII is AGC."[3]

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

Core promoters

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

"The core promoter is the minimal portion of the promoter required to properly initiate gene transcription.[4]"[5]

It contains a binding site for RNA polymerase (RNA polymerase I, RNA polymerase II, or RNA polymerase III).

"[T]he core promoter [consists of] the DNA sequences, which encompass the transcription start site (within about -40 and +40 [nucleotides] relative to the +1 start site"[6].

"Several factors have been identified that bind to core promoters (reviewed in Smale, 1997)"[7][8].

A core promoter that contains all three subelements of the downstream core element may be much less common than one containing only one or two.[3] "SI resides approximately from +6 to +11, SII from +16 to +21, and SIII from +30 to +34."[3]

Transcription start sites

Notation: let the subscript (+1) indicate the specific nucleobase (nucleotide) along the template strand that is a transcription start site. For example, A+1.

The transcription start site (TSS) is the location on the DNA template strand where transcription begins at the 3'-end of a gene.[9] This location corresponds to the 5'-end of the mRNA which by convention is used to designate DNA locations.[9]

Nucleotides downstream from the TSS (N+1, where N stands for any nucleotide) are numbered increasing from +1.

TSS location

One method to perform a TSS location is to test for portions of the downstream core element (DCE) within the about to be transcribed portion of the gene.

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.[3]

Transcription factor II D

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.[3] TFIID probably serves as a core promoter recognition complex.[3]

TAF1 interacts with the DCE in a sequence-dependent manner.[3]

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

  1. "TATA- and DPE-dependent promoters are specific for particular enhancers"[3],
  2. "preferences of activators for specific core promoter architectures"[3], 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."[3]

Research

Hypothesis:

  1. The downstream core element is not involved in the transcription of A1BG.

Control groups

This is an image of a Lewis rat. Credit: Charles River Laboratories.

The findings demonstrate a statistically systematic change from the status quo or the control group.

“In the design of experiments, treatments [or special properties or characteristics] are applied to [or observed in] experimental units in the treatment group(s).[10] In comparative experiments, members of the complementary group, the control group, receive either no treatment or a standard treatment.[11]"[12]

Proof of concept

Def. a “short and/or incomplete realization of a certain method or idea to demonstrate its feasibility"[13] is called a proof of concept.

Def. evidence that demonstrates that a concept is possible is called proof of concept.

The proof-of-concept structure consists of

  1. background,
  2. procedures,
  3. findings, and
  4. interpretation.[14]

See also

References

  1. ↑ "downstream, In: Wiktionary". San Francisco, California: Wikimedia Foundation, Inc. August 30, 2012. Retrieved 2013-06-28.
  2. ↑ "core, In: Wiktionary". San Francisco, California: Wikimedia Foundation, Inc. June 18, 2013. Retrieved 2013-06-28.
  3. 1 2 3 4 5 6 7 8 9 10 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.
  4. ↑ 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.lps.ens.fr/~monasson/Houches/Kadonaga/CorePromoterAnnuRev2003.pdf. Retrieved 2012-05-07.
  5. ↑ "Promoter (genetics), In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. December 30, 2012. Retrieved 2013-01-01.
  6. ↑ Thomas W. Burke and James T. Kadonaga (November 15, 1997). "The downstream core promoter element, DPE, is conserved from Drosophila to humans and is recognized by TAFII60 of Drosophila". Genes & Development 11 (22): 3020–31. doi:10.1101/gad.11.22.3020. PMID 9367984. PMC 316699. http://genesdev.cshlp.org/content/11/22/3020.long.
  7. ↑ Gillian E. Chalkley and C. Peter Verrijzer (September 1, 1999). "DNA binding site selection by RNA polymerase II TAFs: a TAFII250-TAFII150 complex recognizes the Initiator". The EMBO Journal 18 (17): 4835-45. PMID 10469661. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1171555/pdf/004835.pdf. Retrieved 2012-04-26.
  8. ↑ S. T. Smale (1997). "Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes". Biochim. Biophys. Acta. 1351: 73-88.
  9. 1 2 Marketa J. Zvelebil, Jeremy O. Baum (2008). Dom Holdsworth. ed. Understanding bioinformatics. New York: Garland Science. pp. 772. ISBN 978-0815340249. http://books.google.com/books?id=dGayL_tdnBMC&printsec=frontcover&dq=Understanding+bioinformatics&hl=en.
  10. ↑ Klaus Hinkelmann, Oscar Kempthorne (2008). Design and Analysis of Experiments, Volume I: Introduction to Experimental Design (2nd ed.). Wiley. ISBN 978-0-471-72756-9. http://books.google.com/?id=T3wWj2kVYZgC&printsec=frontcover.
  11. ↑ R. A. Bailey (2008). Design of comparative experiments. Cambridge University Press. ISBN 978-0-521-68357-9. http://www.cambridge.org/uk/catalogue/catalogue.asp?isbn=9780521683579.
  12. ↑ "Treatment and control groups, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. May 18, 2012. Retrieved 2012-05-31.
  13. ↑ "proof of concept, In: Wiktionary". San Francisco, California: Wikimedia Foundation, Inc. November 10, 2012. Retrieved 2013-01-13.
  14. ↑ Ginger Lehrman and Ian B Hogue, Sarah Palmer, Cheryl Jennings, Celsa A Spina, Ann Wiegand, Alan L Landay, Robert W Coombs, Douglas D Richman, John W Mellors, John M Coffin, Ronald J Bosch, David M Margolis (August 13, 2005). "Depletion of latent HIV-1 infection in vivo: a proof-of-concept study". Lancet 366 (9485): 549-55. doi:10.1016/S0140-6736(05)67098-5. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1894952/. Retrieved 2012-05-09.

Further reading

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