Angiotensinogen core promoter element gene transcriptions

Editor-In-Chief: Henry A. Hoff

This is a restored image of a group of Ainu men between 1863 and early 1870s. Credit: Felice Beato.

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]

"Sequence analysis of the 5'-flanking region of the human AGT gene revealed the existence of several putative regulatory elements like AGCE2 (human angiotensinogen core promoter element 2), AGCE1 (human angiotensinogen core promoter element 1), 5'-AGCE2, glucocorticoid responsive elements, estrogen responsive element, heat shock responsive element, cAMP responsive elements (Kim, 1995; Yanai et aI., 1996, 1997a, b)."^[2]

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."^[3]

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.^[4]

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."^[3]

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.

AGCE samplings

Copying a responsive elements consensus sequence (A/C)T(C/T)GTG and putting the sequence in "⌘F" finds none between ZNF497 and A1BG or none between ZSCAN22 and A1BG as can be found by the computer programs.

For the Basic programs testing consensus sequence (A/C)T(C/T)GTG (starting with SuccessablesAGCE.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 (+), the programs are, are looking for, and found:

negative strand, negative direction: 4, CTCGTG at 3914, CTTGTG at 3669, ATCGTG at 2096, ATTGTG at 340.
positive strand, negative direction: 0.
positive strand, positive direction: 6, CTCGTG at 3739, CTTGTG at 3095, CTCGTG at 1627, CTCGTG at 1207, CTCGTG at 955, CTCGTG at 855.
negative strand, positive direction: 2, CTCGTG at 4376, ATTGTG at 2679.
inverse complement, negative strand, negative direction: 2, CACGAG at 4403, CACGAT at 336.
inverse complement, positive strand, negative direction: 10, CACGAG at 4472, CACAAG at 3634, CACAAT at 3515, CACGAG at 3232, CACAAG at 2244, CACAAT at 1721, CACGAG at 1182, CACGAG at 708, CACGAG at 572, CACGAG at 435.
inverse complement, positive strand, positive direction, looking for TTTTTTTT, 0.
inverse complement, negative strand, positive direction, looking for TTTTTTTT, 0.

AAA (4560-2846) UTRs

AAA negative direction (2846-2811) core promoters

AAA positive direction (4445-4265) core promoters

AAA negative direction (2811-2596) proximal promoters

AAA positive direction (4265-4050) proximal promoters

AAA negative direction (2596-1) distal promoters

AAA positive direction (4050-1) distal promoters

Acknowledgements

The content on this page was first contributed by: Henry A. Hoff.

Initial content for this page in some instances came from Wikiversity.

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 (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. Retrieved 2012-02-20. Unknown parameter |month= ignored (help)
↑ H. Schmidt, F. Fazekas, and R. Schmidt (2002). Jellinger K.A., Schmidt R., Windisch M., ed. "Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology, In: Ageing and Dementia Current and Future Concepts". 62. Vienna: Springer: 53–9. doi:10.1007/978-3-7091-6139-5_5. ISBN 978-3-211-83796-2. Retrieved 12 February 2020.
↑ ^3.0 ^3.1 Kazuyuki Yanai, Tomoko Saito, Keiko Hirota, Hideyuki Kobayashi, Kazuo Murakami and Akiyoshi Fukamizu (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. Retrieved 2012-02-20. Unknown parameter |month= ignored (help)
↑ HGNC (February 7, 2013). AGT angiotensinogen (serpin peptidase inhibitor, clade A, member 8) [ Homo sapiens ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-02-10.

External links

{{Phosphate biochemistry}}

[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 (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. Retrieved 2012-02-20. Unknown parameter |month= ignored (help)

[Schmidt-2] H. Schmidt, F. Fazekas, and R. Schmidt (2002). Jellinger K.A., Schmidt R., Windisch M., ed. "Microangiopathy-related cerebral damage and angiotensinogen gene: from epidemiology to biology, In: Ageing and Dementia Current and Future Concepts". 62. Vienna: Springer: 53–9. doi:10.1007/978-3-7091-6139-5_5. ISBN 978-3-211-83796-2. Retrieved 12 February 2020.

[Yanai-3] 3.0 ^3.1 Kazuyuki Yanai, Tomoko Saito, Keiko Hirota, Hideyuki Kobayashi, Kazuo Murakami and Akiyoshi Fukamizu (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. Retrieved 2012-02-20. Unknown parameter |month= ignored (help)

[HGNC183-4] HGNC (February 7, 2013). AGT angiotensinogen (serpin peptidase inhibitor, clade A, member 8) [ Homo sapiens ]. 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 2013-02-10.

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