# 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: "S$_I$ is CTTC, S$_{II}$ is CTGT, and S$_{III}$ 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. "S$_I$ resides approximately from +6 to +11, S$_{II}$ from +16 to +21, and S$_{III}$ 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.
S$_I$ as 3'-CTTC-5' can occur as 3 of 4 (CTT, TTC) or 4 of 4 (CTTC). S$_{II}$ as 3'-CTGT-5' can also occur as 3 of 4 (CTG, TGT) or 4 of 4 (CTGT). S$_{III}$ as AGC is not known to vary.
DCE S$_{III}$ 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 S$_{III}$ of the DCE suggesting a critical spacing parameter between S$_{III}$ 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
* "TATA- and DPE-dependent promoters are specific for particular enhancers",
* "preferences of activators for specific core promoter architectures", and
* "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

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