Gene transcriptions/Elements/Downstream cores

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

Downstream
Def. lower "down, in relation to a river or stream ... [f]ollowing the path of a river or stream" 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. the "central part ... heart ... center or inner part ... [t]he most important part of a thing ... [an] inside" is called a core.

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

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

Core promoters
The core promoter is the minimal portion of the promoter required to properly initiate gene transcription.

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".

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

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. "SI resides approximately from +6 to +11, SII from +16 to +21, and SIII from +30 to +34."

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. This location corresponds to the 5'-end of the mRNA which by convention is used to designate DNA locations.

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.

General transcription factor II Ds
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. TFIID probably serves as a core promoter recognition complex.

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

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


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

Hypotheses

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