Gene transcriptions/Initiator elements

< Gene transcriptions

In the biosynthesis of any human protein, the gene that contains the nucleotide sequence which is translated into that protein must be transcribed. For RNA polymerase II holoenzyme to transcribe the gene, the gene's promoter must be located. After the promoter is located, the transcription start site (TSS) is pinpointed by using nucleotide sequences that include the TSS. Within the promoter, most human genes lack a TATA box and have an initiator element (Inr) or downstream promoter element instead.

On the basis of descriptions available, various Inrs are located to test whether the known TSS is located.

Notations

Notation: let the symbol Inr denote an initiator element.

Notation: let the symbol +1 designate the nucleotide that is the transcription start site (TSS).

RNA polymerase II

"RNA pol II itself recognizes features of the Inr which might assist the correct positioning of the polymerase on the promoter (Carcamo et al., 1991; Weis and Reinberg, 1997)."[1][2][3]

RNA polymerase II may form a stable complex on TATA-less promoters that contain Inr elements and possess a weak, intrinsic preference for Inr-like sequences.[2]

Consensus sequences

As in other metazoans, for genes lacking a TATA box, the Inr is functionally analogous, with a base pair (bp) consensus 5'-YYA+1NWYY-3', to direct transcription initiation.[4] Using the degenerate nucleotide code, the consensus sequence is 5'-C/T-C/T-A-A/C/G/T-A/T-C/T-C/T-3', or in the direction of transcription on the template strand: 3'-C/T-C/T-A-A/C/G/T-A/T-C/T-C/T-5'.

"TATA-less core promoters that lack AT-rich sequences in the -30 region and do not stably bind TBP are likely to assemble PICs via alternative pathways and to be regulated by distinct mechanisms (Smale and Kadonaga, 2003). However, the number of such bona fide TATA-less genes remains unclear in eukaryotic genomes."[5]

In Entamoeba histolytica, the consensus sequence is AAAAATTCA.[6]

Enhancers

An Inr for mammalian RNA polymerase II can be defined as a DNA sequence element that overlaps a TSS and is sufficient for

  1. determining the start site location in a promoter that lacks a TATA box and
  2. enhancing the strength of a promoter that contains a TATA box.[7]

TAFs

"Although any isolated TAF may not exhibit sequence-specific interactions at the Inr element in the absence of a TATA-box, a combination of TAFs may bind sequence specifically to the Inr element regardless of the TATA-box and/or DPE (Chalkley and Verrijzer, 1999)."[8] Bold added.

TAF1 "binds to core promoter sequences encompassing the transcription start site. It also binds to activators and other transcriptional regulators, and these interactions affect the rate of transcription initiation."[9]

Prior to transcription, stable binding to an Inr occurs by a complex consisting of TAF1 and TAF2.[1]

TATA box-likes

The Inr is the only element in metazoan protein-encoding genes known to be a functional analog of the TATA box, in that it is sufficient for directing accurate transcription initiation in genes that lack TATA boxes.[10]

General transcription factor II A

General transcription factor II A is critical for the cooperative binding of TFIID to the Inr.[11]

General transcription factor II D

The general transcription factor II D (TFIID) "is one of several general transcription factors that make up the RNA polymerase II preinitiation complex.[12] Before the start of transcription, the transcription factor II D (TFIID) complex, binds to the ... core promoter of the gene."[13]

"TFIID is the first protein to bind to DNA during the formation of the pre-initiation transcription complex of RNA polymerase II (RNA Pol II)."[14]

General transcription factor II I

General transcription factor II I, or TFII-I, is a factor capable of binding the Inr element.[15][16]

Transcription start sites

Usually the Inr contains the TSS.

"[T]he initiator (INR) element located at, or immediately adjacent to, the TSS, ... is recognized by the TBP-associated factors TAF1 and TAF2 of the TFIID complex"[5].

"[T]ranscription does not need to begin at the +1 nucleotide for the Inr to function. RNA polymerase II has been redirected to alternative start sites by reducing ATP concentrations within a nuclear extract, by altering the spacing between the TATA and Inr in a promoter containing both elements, and by dinucleotide initiation strategies".[17]

Research

Hypothesis:

  1. A1BG is not transcribed by an initiator element.

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).[18] In comparative experiments, members of the complementary group, the control group, receive either no treatment or a standard treatment.[19]"[20]

Proof of concept

Def. a “short and/or incomplete realization of a certain method or idea to demonstrate its feasibility"[21] 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.[22]

See also

References

  1. 1 2 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/pubmed/10469661. Retrieved 2012-04-26.
  2. 1 2 J. Carcamo, L. Buckbinder, D. Reinberg (1991). Proceedings of the National Academy of Sciences USA 88: 8052-6.
  3. ↑ L. Weis and D. Reinberg (1997). "Accurate positioning of RNA polymerase II on a natural TATA-less promoter is independent of TATA-binding protein associated factors and initiator-binding proteins". Mol. Cell. Biol. 17: 2973-84.
  4. ↑ DR Liston, PJ Johnson (March 1999). "Analysis of a Ubiquitous Promoter Element in a Primitive Eukaryote: Early Evolution of the Initiator Element". Molecular and Cellular Biology 19 (3): 2380-8. PMID 10022924.
  5. 1 2 C Yang, E Bolotin, T Jiang, FM Sladek, E Martinez (March 2007). "Prevalence of the initiator over the TATA box in human and yeast genes and identification of DNA motifs enriched in human TATA-less core promoters". Gene 389 (1): 52–65. doi:10.1016/j.gene.2006.09.029. PMID 17123746. PMC 1955227. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1955227/?tool=pubmed.
  6. ↑ JE Purdy, BJ Mann, LT Pho, WA Petri Jr (July 19, 1994). "Transient transfection of the enteric parasite Entamoeba histolytica and expression of firefly luciferase". Proceedings of the National Academy of Science USA 91 (15): 7099-103. PMID 8041752. http://www.pnas.org/cgi/pmidlookup?view=long&pmid=8041752. Retrieved 2012-06-10.
  7. ↑ R. Javahery, A. Khachi, K. Lo, B. Zenzie-Gregory, S. T. Smale (January 1994). "DNA Sequence Requirements for Transcriptional Initiator Activity in Mammalian Cells". Molecular and Cellular Biology 14 (1): 116-27. PMID 8264580.
  8. ↑ Ananda L. Roy (August 2001). "Biochemistry and biology of the inducible multifunctional transcription factor TFII-I". Gene 274 (1-2): 1-13. doi:10.1016/S0378-1119(01)00625-4. http://www.sciencedirect.com/science/article/pii/S0378111901006254. Retrieved 2012-04-06.
  9. ↑ HGNC:11535 (March 24, 2012). "TAF1 RNA polymerase II, TATA box binding protein (TBP)-associated factor, 250kDa". Bethesda, Maryland: NCBI. Retrieved 2012-04-09.
  10. ↑ ST Smale (March 1997). "Transcription initiation from TATA-less promoters within eukaryotic protein-coding genes". Biochimica & Biophysica Acta 1351 (1-2): 73-88. doi:10.1016/S0167-4781(96)00206-0. PMID 9116046.
  11. ↑ KH Emami, A Jain, ST Smale (1997). Genes Development 11: 3007-19.
  12. ↑ Benjamin Lewin (2004). Genes VIII. Upper Saddle River, NJ: Pearson Prentice Hall. pp. 636–637. ISBN 0-13-144946-X.
  13. ↑ "Transcription factor II D, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. May 7, 2012. Retrieved 2012-05-20.
  14. ↑ "TATA-binding protein, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. May 18, 2012. Retrieved 2012-05-20.
  15. ↑ AL Roy, M Meisterernst, P. Pognonec, RG Roeder (1991). Nature 354: 245-8.
  16. ↑ AL Roy, S. Malik, M. Meisterernst, RG Roeder (1993). 365. pp. 355-9.
  17. ↑ 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.
  18. ↑ 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.
  19. ↑ 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.
  20. ↑ "Treatment and control groups, In: Wikipedia". San Francisco, California: Wikimedia Foundation, Inc. May 18, 2012. Retrieved 2012-05-31.
  21. ↑ "proof of concept, In: Wiktionary". San Francisco, California: Wikimedia Foundation, Inc. November 10, 2012. Retrieved 2013-01-13.
  22. ↑ 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.

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