Gene transcriptions/Elements/Motif tens



The motif ten element (MTE) is a downstream core promoter element.

Consensus sequences
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']. 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'.

Gene expressions
Although it is harder to regulate the transcription of genes with multiple transcription start sites, "variations in the expression of a constitutive gene would be minimized by the use of multiple start sites."

Earlier "studies led to the design of a super core promoter (SCP) that contains a TATA, Inr, MTE, and DPE in a single promoter (Juven-Gershon et al., 2006b). The SCP is the strongest core promoter observed in vitro and in cultured cells and yields high levels of transcription in conjunction with transcriptional enhancers. These findings indicate that gene expression levels can be modulated via the core promoter."

Human genes
"[T]he human sterol C5 desaturase-like (SC5DL; also known as SC5D[, GeneID: 6309] ) promoter (Nishi et al. 2000; Sugawara et al. 2001) has sequences with similarity to the Drosophila Inr and MTE ... but not to the DPE."

Drosophila genes
"[B]y using the JDSA search program (http://www-biology.ucsd.edu/labs/kadonaga/JDSA.html), ... the Drosophila genome database [can be surveyed] for sequences (which are upstream of an open reading frame) that contain a motif 10 consensus from +18 to +29 relative to A+1 of a consensus Inr sequence."

"About 75% of known human disease genes have a recognizable match in the genome of fruit flies, and 50% of fly protein sequences have mammalian homologs."

"Drosophila is being used as a genetic model for several human diseases including the neurodegenerative disorders Parkinson's, Huntington's, spinocerebellar ataxia and Alzheimer's disease. The fly is also being used to study mechanisms underlying [free radical theory] aging and oxidative stress, immunity], diabetes, and cancer, as well as drug abuse."

Gene transcriptions
"From a teleological standpoint, this arrangement [of focused promoters] is consistent with the notion that it would be easier to regulate the transcription of a gene with a single transcription start site than one with multiple start sites."

Transcription factors
"The MTE in the Drosophila Tollo core promoter is recognized by human basal transcription factors. ... The MTE exhibits synergy with the TATA-box as well as weak activity in the absence of the TATA and DPE motifs with human transcription factors."

Focused promoters
"In focused transcription, there is either a single major transcription start site or several start sites within a narrow region of several nucleotides. Focused transcription is the predominant mode of transcription in simpler organisms."

"Focused transcription initiation occurs in all organisms, and appears to be the predominant or exclusive mode of transcription in simpler organisms."

"In vertebrates, focused transcription tends to be associated with regulated promoters".

"The analysis of focused core promoters has led to the discovery of sequence motifs such as the TATA box, BREu (upstream TFIIBrecognition element), Inr (initiator), MTE (motif ten element), DPE (downstream promoter element), DCE (downstream core element), and XCPE1 (Xcore promoter element 1) [...]."

Dispersed promoters
"In dispersed transcription, there are several weak transcription start sites over a broad region of about 50 to 100 nucleotides. Dispersed transcription is the most common mode of transcription in vertebrates. For instance, dispersed transcription is observed in about two-thirds of human genes."

In vertebrates, "dispersed transcription is typically observed in constitutive promoters in CpG islands."

Core promoters
"Focused transcription typically initiates within the Inr, and the A nucleotide in the Inr consensus is usually designed as the “+ 1” position, whether or not transcription actually initiates at that particular nucleotide. This convention is useful because other core promoter motifs, such as the MTE and DPE, function with the Inr in a manner that exhibits a strict spacing dependence with the Inr consensus sequence (and hence, the A + 1 nucleotide) rather than the actual transcription start site (Burke and Kadonaga, 1997, Kutach and Kadonaga, 2000 and Lim et al., 2004)."

Gene transcription elements
Def. one "of the simplest or essential parts or principles of which anything consists, or upon which the constitution or fundamental powers of anything are based" is called an element.

Motif ten elements
The motif ten element (MTE) "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."

"The MTE (motif ten element) was found to be a functionally active core promoter element that corresponds to an overrepresented sequence (termed motif 10) that was identified in Drosophila core promoter regions ( Ohler et al., 2002 and Lim et al., 2004). The MTE is located immediately upstream of the DPE at precisely + 18 to + 27 relative to the A + 1 in the Inr and is conserved from Drosophila to humans. DNase I footprinting analyses suggest that the MTE, like the DPE, is a recognition site for TFIID. The MTE functions cooperatively with the Inr but can act independently of the DPE as well as the TATA box. There is, however, synergy between the MTE and DPE as well as between the MTE and TATA box."

Hypotheses

 * 1) The motif ten element is not used to transcribe A1BG.

Samplings
For the Basic programs (starting with SuccessablesMTE.bas) written to compare nucleotide sequences with the sequences on either the template strand (-), or coding strand (+), of the DNA, in the negative direction (-), or the positive direction (+), including extension of nts from 958 to 4445, the programs are, are looking for, and found:
 * 1) negative strand in the negative direction (from ZSCAN22 to A1BG) is SuccessablesMTE--.bas, looking for 3'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-5', 0,
 * 2) negative strand in the positive direction (from ZNF497 to A1BG) is SuccessablesMTE-+.bas, looking for 3'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-5', 0,
 * 3) positive strand in the negative direction is SuccessablesMTE+-.bas, looking for 3'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-5', 0,
 * 4) positive strand in the positive direction is SuccessablesMTE++.bas, looking for 3'-C-C/G-A-A/G-C-C/G-C/G-A-A-C-G-C/G-5', 0,
 * 5) complement, negative strand, negative direction is SuccessablesMTEc--.bas, looking for 3'-G-C/G-T-C/T-G-C/G-C/G-T-T-G-C-C/G-5', 0,
 * 6) complement, negative strand, positive direction is SuccessablesMTEc-+.bas, looking for 3'-G-C/G-T-C/T-G-C/G-C/G-T-T-G-C-C/G-5', 0,
 * 7) complement, positive strand, negative direction is SuccessablesMTEc+-.bas, looking for 3'-G-C/G-T-C/T-G-C/G-C/G-T-T-G-C-C/G-5', 0,
 * 8) complement, positive strand, positive direction is SuccessablesMTEc++.bas, looking for 3'-G-C/G-T-C/T-G-C/G-C/G-T-T-G-C-C/G-5', 0,
 * 9) inverse complement, negative strand, negative direction is SuccessablesMTEci--.bas, looking for 3'-C/G-C-G-T-T-C/G-C/G-G-C/T-T-C/G-G-5', 0,
 * 10) inverse complement, negative strand, positive direction is SuccessablesMTEci-+.bas, looking for 3'-C/G-C-G-T-T-C/G-C/G-G-C/T-T-C/G-G-5', 0,
 * 11) inverse complement, positive strand, negative direction is SuccessablesMTEci+-.bas, looking for 3'-C/G-C-G-T-T-C/G-C/G-G-C/T-T-C/G-G-5', 0,
 * 12) inverse complement, positive strand, positive direction is SuccessablesMTEci++.bas, looking for 3'-C/G-C-G-T-T-C/G-C/G-G-C/T-T-C/G-G-5', 0,
 * 13) inverse, negative strand, negative direction, is SuccessableMTEi--.bas, looking for 3'-C/G-G-C-A-A-C/G-C/G-C-A/G-A-C/G-C-5', 0,
 * 14) inverse, negative strand, positive direction, is SuccessablesMTEi-+.bas, looking for 3'-C/G-G-C-A-A-C/G-C/G-C-A/G-A-C/G-C-5', 0,
 * 15) inverse, positive strand, negative direction, is SuccessablesMTEi+-.bas, looking for 3'-C/G-G-C-A-A-C/G-C/G-C-A/G-A-C/G-C-5', 0,
 * 16) inverse, positive strand, positive direction, is SuccessablesMTEi++.bas, looking for 3'-C/G-G-C-A-A-C/G-C/G-C-A/G-A-C/G-C-5', 0.