Androgen response element gene transcriptions: Difference between revisions

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Positive strand, positive direction: 5'-ACAAGA-3' at 108 and complement.
Positive strand, positive direction: 5'-ACAAGA-3' at 108 and complement.
Negative strand, negative direction: 5'-TGTTCT-3' at 3759, 5'-TGTTCT-3' at 3635, 5'-TGTTCT-3' at 3340, 5'-TGTTCT-3' at 3307, and complements.
Positive strand, negative direction: 5'-TGTTCT-3' at 45 and complement.
Negative strand, positive direction: 5'-TGTTCT-3' at 108 and complements.
Positive strand, positive direction: 0 and complements.


==Acknowledgements==
==Acknowledgements==

Revision as of 23:06, 3 November 2020

Associate Editor(s)-in-Chief: Henry A. Hoff

"Androgen receptors (ARs) (NR3C4; nuclear receptor subfamily 3, group C, member 4) have a crucial role in the development, function and homeostasis of PCa cells. ARs can be activated as a transcription factor via binding to androgen hormones (either testosterone or dihydrotestosterone). This receptor has two mainfunctional domains: ligand-binding and DNA-binding (DBD).8"[1]

"Androgen response elements structurally consist of a short DNA motif with base sequence specificity within the promoter upstream of the androgen-responsive genes. The HRE contains apair of conserved sequences, which are separated by a three-nucleotide spacer. This sequence is determined as 5'-GGTACAnnnTGTTCT-3'10, 11 with 5'-CGG-3' as the spacer in the androgen response element."[1]

"The androgen response element sequence, 5'-GGTACACGGTGTTCT-3', was obtained from the National Center of Biotechnology Information (NCBI)."[1]

"ARE half sites, benefit from neighboring motifs or cooperating transcription factors in regulating gene expression."[2]

"AREs are well studied but poorly defined and have been shown to contain two hexamers with a three base-pair spacer with an inverted repeat in the second hexamer22."[2]

A "strict ideal 15mer motif search pattern of two hexamers with a 3mer spacer [is] AGAACANNNTGTTCT [...]."[2]

"The ideal 15mer model of AGAACANNNTGTTCT had 71 AREs."[2]

"Using the Jaspar motif database, we grouped significant transcription factor logos within a window of ±160 bp from the ARE with a p-value of less than 0.05. Top hits included forkhead box (FOX), Krüppel-like factors (KLF), basic helix-loop-helix (BHLH), sterol regulatory element binding factor (SREBF), and v-myc avian myelocytomatosis viral oncogene homolog (MYC) families of transcription factors."[2]

"Taken together, the transcription factor network analysis (top hits in motif enrichment with p-values below 0.05) suggests that KLF, MYC, FOX, and SREBF families of transcription factors have the ability to utilize motifs in the cistrome of AREs and to cooperate with the AR."[2]

"Despite a larger number of weaker ARE half sites found in the proximity of KLF motifs, stronger AREs next to KLF motifs resulted in a larger transcriptional response."[2]

"The KLF family recognizing GC/GT boxes has been implicated in regulation of oncogenic expression signatures in LNCaP and PC3 prostate cancer cell lines85,86."[2]

Human genes

Main article: Human genes

Gene ID: 367 is AR androgen receptor aka NR3C4 on Xq12: "The androgen receptor gene is more than 90 kb long and codes for a protein that has 3 major functional domains: the N-terminal domain, DNA-binding domain, and androgen-binding domain. The protein functions as a steroid-hormone activated transcription factor. Upon binding the hormone ligand, the receptor dissociates from accessory proteins, translocates into the nucleus, dimerizes, and then stimulates transcription of androgen responsive genes. This gene contains 2 polymorphic trinucleotide repeat segments that encode polyglutamine and polyglycine tracts in the N-terminal transactivation domain of its protein. Expansion of the polyglutamine tract from the normal 9-34 repeats to the pathogenic 38-62 repeats causes spinal bulbar muscular atrophy (SBMA, also known as Kennedy's disease). Mutations in this gene are also associated with complete androgen insensitivity (CAIS). Alternative splicing results in multiple transcript variants encoding different isoforms."[3]

Gene expressions

Main article: Gene expressions

"Biased expression in liver (RPKM 12.9), endometrium (RPKM 10.8) and 13 other tissues."[3]

Consensus sequences

Main article: Consensus sequence gene transcriptions

5′-GGTACACGGTGTTCT-3′[1]

5'-TGGAGAACAGCCTGTTCTCCA-3' or 5'-AGAACAGCCTGTTCT-3'[2] "Using the identified AREs within our experiment a refined extended canonical ARE model is proposed and deposited in transcription factor databases [...]."[2]

Hypotheses

Main article: Hypotheses
  1. A1BG has no Androgen response elements in either promoter.
  2. A1BG is not transcribed by an Androgen response element.
  3. Androgen response element does not participate in the transcription of A1BG.

Androgen response element (Kouhpayeh) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence 5'-GGTACA-3' 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 5'-GGTACA-3' (starting with SuccessablesAnRE.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:

  1. negative strand, negative direction, looking for 5'-GGTACA-3', 0.
  2. negative strand, positive direction, looking for 5'-GGTACA-3', 0.
  3. positive strand, negative direction, looking for 5'-GGTACA-3', 0.
  4. positive strand, positive direction, looking for 5'-GGTACA-3', 3, 5'-GGTACA-3' at 3901, 5'-GGTACA-3' at 3336, 5'-GGTACA-3' at 2474 and complements.
  5. complement, negative strand, negative direction, looking for 5'-CCATGT-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-CCATGT-3', 3, 5'-CCATGT-3' at 3901, 5'-CCATGT-3' at 3336, 5'-CCATGT-3' at 2474.
  7. complement, positive strand, negative direction, looking for 5'-CCATGT-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-CCATGT-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-TGTACC-3', 3, TGTACC-3' at 2614, 5'-TGTACC-3' at 2152, 5'-TGTACC-3' at 1207 and complements.
  10. inverse complement, negative strand, positive direction, looking for 5'-TGTACC-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-TGTACC-3', 1, 5'-TGTACC-3' at 798 and complement.
  12. inverse complement, positive strand, positive direction, looking for 5'-TGTACC-3', 1, 5'-TGTACC-3' at 2032.
  13. inverse negative strand, negative direction, looking for 5'-ACATGG-3', 1, 5'-ACATGG-3' at 798.
  14. inverse negative strand, positive direction, looking for 5'-ACATGG-3', 1, 5'-ACATGG-3' at 2032.
  15. inverse positive strand, negative direction, looking for 5'-ACATGG-3', 3, 5'-ACATGG-3' at 2614, 5'-ACATGG-3' at 2152, 5'-ACATGG-3' at 1207.
  16. inverse positive strand, positive direction, looking for 5'-ACATGG-3', 0.

Looking for the half site of 5'-TGTTCT-3':

For the Basic programs testing consensus sequence 5'-TGTTCT-3' (starting with SuccessablesAnRE2.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:

  1. negative strand, negative direction, looking for 5'-TGTTCT-3', 4, 5'-TGTTCT-3' at 3759, 5'-TGTTCT-3' at 3635, 5'-TGTTCT-3' at 3340, 5'-TGTTCT-3' at 3307, and complements.
  2. negative strand, positive direction, looking for 5'-TGTTCT-3', 1, 5'-TGTTCT-3' at 108 and complement.
  3. positive strand, negative direction, looking for 5'-TGTTCT-3', 1, 5'-TGTTCT-3' at 45 and complement.
  4. positive strand, positive direction, looking for 5'-TGTTCT-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-ACAAGA-3', 1, 5'-ACAAGA-3' at 45.
  6. complement, negative strand, positive direction, looking for 5'-ACAAGA-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-ACAAGA-3', 4, 5'-ACAAGA-3' at 3759, 5'-ACAAGA-3' at 3635, 5'-ACAAGA-3' at 3340, 5'-ACAAGA-3' at 3307.
  8. complement, positive strand, positive direction, looking for 5'-ACAAGA-3', 1, 5'-ACAAGA-3' at 108.
  9. inverse complement, negative strand, negative direction, looking for 5'-AGAACA-3', 1, 5'-AGAACA-3' at 281 and complement.
  10. inverse complement, negative strand, positive direction, looking for 5'-AGAACA-3', 2, 5'-AGAACA-3' at 4068, 5'-AGAACA-3' at 3094 and complements.
  11. inverse complement, positive strand, negative direction, looking for 5'-AGAACA-3', 2, 5'-AGAACA-3' at 3668, 5'-AGAACA-3' at 287 and complement.
  12. inverse complement, positive strand, positive direction, looking for 5'-AGAACA-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-TCTTGT-3', 2, 5'-TCTTGT-3' at 3668, 5'-TCTTGT-3' at 287.
  14. inverse negative strand, positive direction, looking for 5'-TCTTGT-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-TCTTGT-3', 1, 5'-TCTTGT-3' at 281.
  16. inverse positive strand, positive direction, looking for 5'-TCTTGT-3', 2, 5'-TCTTGT-3' at 4068, 5'-TCTTGT-3' at 3094.

AnRE (Kouhpayeh) proximal promoters

Negative strand, positive direction: 5'-AGAACA-3' at 4068, and complement.

AnRE (Kouhpayeh) distal promoters

Main article: Distal promoter gene transcriptions

Negative strand, negative direction: 5'-TGTTCT-3' at 3759, 5'-TGTTCT-3' at 3635, 5'-TGTTCT-3' at 3340, 5'-TGTTCT-3' at 3307, TGTACC-3' at 2614, 5'-TGTACC-3' at 2152, 5'-TGTACC-3' at 1207, 5'-ACATGG-3' at 798, 5'-AGAACA-3' at 281 and complements.

Positive strand, negative direction: 5'-AGAACA-3' at 3668, 5'-AGAACA-3' at 287, 5'-TGTTCT-3' at 45 and complement.

Negative strand, positive direction: 5'-AGAACA-3' at 3094, 5'-TGTTCT-3' at 108 and complements.

Positive strand, positive direction: 5'-GGTACA-3' at 3901, 5'-GGTACA-3' at 3336, 5'-GGTACA-3' at 2474, 5'-TGTACC-3' at 2032, 5'-ACAAGA-3' at 108 and complements.

Note: negative strand, negative direction has 5'-TGTTCT-3' at 3340, while positive strand, positive direction has 5'-GGTACA-3' at 3336, negative strand, positive direction has 5'-CCATGT-3' at 3336, and positive strand, negative direction has 5'-ACAAGA-3' at 3340.

Looking for full AnRE (Kouhpayeh)

  1. positive strand, positive direction, looking for 5'-GGTACANNNTGTTCT-3', 0.
  2. inverse complement, negative strand, negative direction, looking for 5'-AGAACANNNTGTACC-3', 0.
  3. inverse negative strand, negative direction, looking for 5'-TCTTGTNNNACATGG-3', 0.
  4. inverse negative strand, positive direction, looking for 5'-TCTTGTNNNACATGG-3', 0.

Androgen response element (Wilson) samplings

Main article: Model samplings

Copying a responsive elements consensus sequence 5'-TGATTCGTGAG-3' 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. Ideal consensus sequence is 5'-AGAACANNNTGTTCT-3'.[2]

For the Basic programs testing consensus sequence 5'-AGAACANNNTGTTCT-3' (starting with SuccessablesAAA.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:

  1. negative strand, negative direction, looking for 5'-AGAACANNNTGTTCT-3', 0.
  2. negative strand, positive direction, looking for 5'-AGAACANNNTGTTCT-3', 0.
  3. positive strand, negative direction, looking for 5'-AGAACANNNTGTTCT-3', 0.
  4. positive strand, positive direction, looking for 5'-AGAACANNNTGTTCT-3', 0.
  5. complement, negative strand, negative direction, looking for 5'-TCTTGTNNNACAAGA-3', 0.
  6. complement, negative strand, positive direction, looking for 5'-TCTTGTNNNACAAGA-3', 0.
  7. complement, positive strand, negative direction, looking for 5'-TCTTGTNNNACAAGA-3', 0.
  8. complement, positive strand, positive direction, looking for 5'-TCTTGTNNNACAAGA-3', 0.
  9. inverse complement, negative strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  10. inverse complement, negative strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  11. inverse complement, positive strand, negative direction, looking for 5'-TTTTTTTT-3', 0.
  12. inverse complement, positive strand, positive direction, looking for 5'-TTTTTTTT-3', 0.
  13. inverse negative strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  14. inverse negative strand, positive direction, looking for 5'-AAAAAAAA-3', 0.
  15. inverse positive strand, negative direction, looking for 5'-AAAAAAAA-3', 0.
  16. inverse positive strand, positive direction, looking for 5'-AAAAAAAA-3', 0.

AnRE (Wilson) core promoters

Main article: Core promoter gene transcriptions

AAA (Wilson) proximal promoters

Main article: Proximal promoter gene transcriptions

Negative strand, positive direction: 5'-AGAACA-3' at 4068, and complement.

AnRE (Wilson) distal promoters

Main article: Distal promoter gene transcriptions

Negative strand, negative direction: 5'-AGAACA-3' at 281 and complement.

Positive strand, negative direction: 5'-AGAACA-3' at 3668, 5'-AGAACA-3' at 287 and complements.

Negative strand, positive direction: 5'-AGAACA-3' at 3094 and complement.

Positive strand, positive direction: 5'-ACAAGA-3' at 108 and complement.

Negative strand, negative direction: 5'-TGTTCT-3' at 3759, 5'-TGTTCT-3' at 3635, 5'-TGTTCT-3' at 3340, 5'-TGTTCT-3' at 3307, and complements.

Positive strand, negative direction: 5'-TGTTCT-3' at 45 and complement.

Negative strand, positive direction: 5'-TGTTCT-3' at 108 and complements.

Positive strand, positive direction: 0 and complements.

Acknowledgements

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

See also

References

  1. ↑ 1.0 1.1 1.2 1.3 S Kouhpayeh, AR Einizadeh, Z Hejazi, M Boshtam, L Shariati, M Mirian, L Darzi, M Sojoudi, H Khanahmad and A Rezaei (1 July 2016). "Antiproliferative effect of a synthetic aptamer mimicking androgen response elements in the LNCaP cell line" (PDF). Cancer Gene Therapy. 23: 254–257. doi:10.1038/cgt.2016.26. Retrieved 3 October 2020.
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 Stephen Wilson, Jianfei Qi & Fabian V. Filipp (14 September 2016). "Refinement of the androgen response element based on ChIP-Seq in androgen-insensitive and androgen-responsive prostate cancer cell lines". Scientific Reports. 6: 32611. doi:10.1038/srep32611. Retrieved 3 October 2020.
  3. ↑ 3.0 3.1 RefSeq (January 2017). "AR androgen receptor [ Homo sapiens (human) ]". 8600 Rockville Pike, Bethesda MD, 20894 USA: National Center for Biotechnology Information, U.S. National Library of Medicine. Retrieved 1 November 2020.

External links

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