Evidence map›Paper›PMID 19908860›Full record

ArticleJournal of the American Chemical Society2009

The i-motif in the bcl-2 P1 promoter forms an unexpectedly stable structure with a unique 8:5:7 loop folding pattern.

Samantha Kendrick, Yoshitsugu Akiyama, Sidney M Hecht, Laurence H Hurley

Abstract read
In one paragraph

Article in Journal of the American Chemical Society, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
2.0field-weighted citation impact, top 14% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

56 citing papers in PubMed, 149 citations in OpenAlex.

  1. Review
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  7. Biological Regulation StudiedAccounts of chemical research · 2025
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Non-canonical DNA structures in the human ribosomal DNA.Histochemistry and cell biology · 2023
    Review
  13. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

4 authors at 2 institutions in 1 country.

Samantha KendrickArizona Cancer Center, 1515 North Campbell Avenue, Tucson, Arizona 85724, USA.
Yoshitsugu Akiyama
Sidney M Hecht
Laurence H Hurley
University of Arizona · USArizona State University · US

Funding

VITAMIN AP30CA023074 · NCI · UNIVERSITY OF ARIZONA · PI Dan Theodorescu · 1985 to 2026
$110.2M
Integrative Cancer Scholars Training GrantT32CA009213 · NCI · UNIVERSITY OF ARIZONA · PI CAREW, JENNIFER S, CURIEL-LEWANDROWSKI, CLARA · 1985 to 2024
$8.6M
Establishing a molecular system for drug targeting of transcriptional controlR01GM085585 · NIGMS · UNIVERSITY OF ARIZONA · PI HURLEY, LAURENCE H. · 2008 to 2011
$1.5M
NCI NIH HHS P30 CA023074NCI NIH HHS T32 CA009213NCI NIH HHS T32CA09213NIGMS NIH HHS GM085585NIGMS NIH HHS R01 GM085585
6 · The paper itself

Abstract

Transcriptional regulation of the bcl-2 proto-oncogene is highly complex, with the majority of transcription driven by the P1 promoter site and the interaction of multiple regulatory proteins. A guanine- and cytosine-rich (GC-rich) region directly upstream of the P1 site has been shown to be integral to bcl-2 promoter activity, as deletion or mutation of this region significantly increases transcription. This GC-rich element consists of six contiguous runs of guanines and cytosines that have the potential to adopt DNA secondary structures, the G-quadruplex and i-motif, respectively. Our laboratory has previously demonstrated that the polypurine-rich strand of the bcl-2 promoter can form a mixture of three different G-quadruplex structures. In this current study, we demonstrate that the complementary polypyrimidine-rich strand is capable of forming one major intramolecular i-motif DNA secondary structure with a transition pH of 6.6. Characterization of the i-motif folding pattern using mutational studies coupled with circular dichroic spectra and thermal stability analyses revealed an 8:5:7 loop conformation as the predominant structure at pH 6.1. The folding pattern was further supported by chemical footprinting with bromine. In addition, a novel assay involving the sequential incorporation of a fluorescent thymine analog at each thymine position provided evidence of a capping structure within the top loop region of the i-motif. The potential of the GC-rich element within the bcl-2 promoter region to form DNA secondary structures suggests that the transition from the B-DNA to non-B-DNA conformation may play an important role in bcl-2 transcriptional regulation. Furthermore, the two adjacent large lateral loops in the i-motif structure provide an unexpected opportunity for protein and small molecule recognition.

Indexed as

GC Rich SequenceBase PairingBase SequenceBromineCircular DichroismDeoxyuridineDNADNA Mutational AnalysisFluorescent DyesHumansHydrogen-Ion ConcentrationMolecular Sequence DataMutationPromoter Regions, GeneticProto-Oncogene MasProto-Oncogene Proteins c-bcl-2BromineDeoxyuridineDNAFluorescent DyesMAS1 protein, humanProto-Oncogene MasProto-Oncogene Proteins c-bcl-2Thymine

Identifiers

PMID19908860
PMCPMC2787777
OpenAlexW2086622557

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.