Gene transcriptions/Elements/Angiotensinogen core promoters

Angiotensinogen core promoter element 1 (AGCE1) is an example of a core promoter element that may occur in a DNA sequence for only one gene (the human angiotensinogen gene angiotensin).

Proof of concept

For the original research project focused on the transcription of A1BG, proof of concept may be simply that AGCE1 occurs in the core promoter.

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). Any specific gene’s core promoter is ultimately targeted by a vast network of regulatory factors that contribute to the initiation of transcription by RNA polymerase.

AGCE1 can occur upstream from -25 to -1 base pairs (bp)s of the transcription start site.^[1]

Consensus sequences

The consensus sequence is 3'-A/C-T-C/T-5'.^[1] By convention, this is 5'-MTY-3' on the mRNA, with T replaced by uracil (U).

The core nucleotides for AGCE1 include 3'-A/C-T-C/T-G-T-G-5', "located between the TATA box and transcription initiation site (positions −25 to −1) is an authentic regulator of human AG transcription."^[2]

Human genes

"[T]he core promoter element 1 (AGCE1) of the human angiotensinogen gene (AGT) ... acts as a critical regulator of AGT transcription".^[1] GeneID: 183 angiotensinogen (serpin peptidase inhibitor, clade A, member 8) [ Homo sapiens ] has the official symbol AGT.^[3]

Gene transcriptions

Within the variation allowed by the consensus sequence, it is likely that the transcriptional activities of an E-box-like motif of two juxtaposed AGCE1 elements have the following ratios: "CTC/CTC and ATC/ATC homozygotes or the CTC/ATC heterozygotes are 2.5 times higher than that of the ATT/ATT homozygote and that the CTC/ATT and ATC/ATT heterozygotes are 1.75 times higher than that of the ATT/ATT homozygote."^[2]

Angiotensinogen

The diagram consists of spacefilling models of angiotensin I (left) and angiotensin II (right). Credit: Fvasconcellos.

This diagram describes the stages in the renin-angiotensin-aldosterone system. Credit: A. Rad.

Angiotensinogen is an α-2-globulin produced constitutively and released into the circulation mainly by the liver. It is a member of the serpin family, although it is not known to inhibit other enzymes, unlike most serpins. Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.

Angiotensin I ([CAS registry number] CAS# 11128-99-7) is formed by the action of renin on angiotensinogen. Renin cleaves the peptide bond between the leucine (Leu) and valine (Val) residues on angiotensinogen, creating the ten-amino acid peptide (des-Asp) angiotensin I. Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE, or kinase).

A1BG gene transcriptions

An AGCE1 occurs at 3'-ATC-5', in the nucleotides before the transcription start site for the transcription of A1BG, which ends 5 bp upstream from the TSS and is the only AGCE1 within -25 and -1 bp of the TSS. Usually, the AGCE1 spans -20 to -18 bp, when a TATA box is present.^[1]

However, for the transcription of A1BG, there is no TATA box and the core nucleotides 3'-GTG-5' do not occur on either side of 3'-ATC-5'.

Hypotheses

AGCE1 does not participate in the transcription of A1BG.

References

↑ ^1.0 ^1.1 ^1.2 ^1.3 Noriyuki Sato; Tomohiro Katsuya; Hiromi Rakugi; Seiju Takami; Yukiko Nakata; Tetsuro Miki; Jitsuo Higaki; Toshio Ogihara (September 1997). "Association of Variants in Critical Core Promoter Element of Angiotensinogen Gene With Increased Risk of Essential Hypertension in Japanese". Hypertension 30 (3 Pt 1): 321-5. doi:10.1161/01.HYP.30.3.321. PMID 9314411. http://www.ncbi.nlm.nih.gov/pubmed/9314411. Retrieved 2012-02-20.
↑ ^2.0 ^2.1 Kazuyuki Yanai, Tomoko Saito, Keiko Hirota, Hideyuki Kobayashi, Kazuo Murakami and Akiyoshi Fukamizu (28 November 1997). "Molecular Variation of the Human Angiotensinogen Core Promoter Element Located between the TATA Box and Transcription Initiation Site Affects Its Transcriptional Activity". The Journal of Biological Chemistry 272 (48): 30558-62. PMID 9374551. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9374551. Retrieved 2012-02-20.
↑ HGNC (February 7, 2013). AGT angiotensinogen (serpin peptidase inhibitor, clade A, member 8) ( Homo sapiens ). Bethesda, MD, USA: National Center for Biotechnology Information, U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/gene/183. Retrieved 2013-02-10.

External links

[Sato-1] 1.0 ^1.1 ^1.2 ^1.3 Noriyuki Sato; Tomohiro Katsuya; Hiromi Rakugi; Seiju Takami; Yukiko Nakata; Tetsuro Miki; Jitsuo Higaki; Toshio Ogihara (September 1997). "Association of Variants in Critical Core Promoter Element of Angiotensinogen Gene With Increased Risk of Essential Hypertension in Japanese". Hypertension 30 (3 Pt 1): 321-5. doi:10.1161/01.HYP.30.3.321. PMID 9314411. http://www.ncbi.nlm.nih.gov/pubmed/9314411. Retrieved 2012-02-20.

[Yanai-2] 2.0 ^2.1 Kazuyuki Yanai, Tomoko Saito, Keiko Hirota, Hideyuki Kobayashi, Kazuo Murakami and Akiyoshi Fukamizu (28 November 1997). "Molecular Variation of the Human Angiotensinogen Core Promoter Element Located between the TATA Box and Transcription Initiation Site Affects Its Transcriptional Activity". The Journal of Biological Chemistry 272 (48): 30558-62. PMID 9374551. http://www.jbc.org/cgi/pmidlookup?view=long&pmid=9374551. Retrieved 2012-02-20.

[HGNC183-3] HGNC (February 7, 2013). AGT angiotensinogen (serpin peptidase inhibitor, clade A, member 8) ( Homo sapiens ). Bethesda, MD, USA: National Center for Biotechnology Information, U.S. National Library of Medicine. http://www.ncbi.nlm.nih.gov/gene/183. Retrieved 2013-02-10.

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