Evidence map›Paper›PMID 16263792›Full record

ArticleBlood2006

Repression of human gamma-globin gene expression by a short isoform of the NF-E4 protein is associated with loss of NF-E2 and RNA polymerase II recruitment to the promoter.

Quan Zhao, Wenlai Zhou, Gerhard Rank, Rosemary Sutton, Xi Wang, Helen Cumming, Loretta Cerruti, John M Cunningham, Stephen M Jane

Open access · bronzeAbstract read
In one paragraph

Article in Blood, 2006. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
0.6field-weighted citation impact, top 34% 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

15 citing papers in PubMed, 34 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Identification of a 5-Gene Signature Predicting Progression and Prognosis of Clear Cell Renal Cell Carcinoma.Medical science monitor : international medical journal of experimental and clinical research · 2019
    Article
  5. Regulation of the fetal hemoglobin silencing factor BCL11A.Annals of the New York Academy of Sciences · 2016
    Review
  6. Article
  7. The switch from fetal to adult hemoglobin.Cold Spring Harbor perspectives in medicine · 2013
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
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

9 authors at 3 institutions in 2 countries.

Quan ZhaoRotary Bone Marrow Research Laboratory, Royal Melbourne Hospital Research Foundation, Parkville, Australia.
Wenlai Zhou
Gerhard Rank
Rosemary Sutton
Xi Wang
Helen Cumming
Loretta Cerruti
John M Cunningham
Stephen M Jane
State Key Laboratory of Pharmaceutical BiotechnologyNanjing University · CNSt. Jude Children's Research Hospital · US

Funding

Viral Vector Technology (VVTSR)P30CA021765 · NCI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI CHARLES ROBERTS · 1985 to 2026
$166.9M
VIROSOME/PROTEOLIPOSOME MEDIATED GENE TRANSFERP01HL053749 · NHLBI · ST. JUDE CHILDREN'S RESEARCH HOSPITAL · PI WEISS, MITCHELL J · 1994 to 2022
$43.6M
Role of LBP-1a and p14 NF-E4 in gamma globin gene expre*R01HL069232 · NHLBI · ROYAL MELBOURNE HOSPITAL · PI JANE, STEPHEN M. · 2001 to 2004
$700k
NCI NIH HHS P30 CA 21765NHLBI NIH HHS P01 HL53749-03NHLBI NIH HHS R01 HL69232-01
6 · The paper itself

Abstract

Binding of the stage selector protein (SSP) to the stage selector element (SSE) in the human gamma-globin promoter contributes to the preferential expression of the gamma-gene in fetal erythroid cells. The SSP contains the transcription factor CP2 and an erythroid-specific partner, NF-E4. The NF-E4 gene encodes a 22-kDa polypeptide employing a non-AUG initiation codon. Antisera specific to NF-E4 detects this species and an additional 14 kDa protein, which initiates from an internal methionine. Enforced expression of p14 NF-E4 in the K562 fetal/erythroid cell line, and in primary erythroid cord blood progenitors, results in repression of gamma-gene expression. Biochemical studies reveal that p14 NF-E4 interacts with CP2, resulting in diminished association of CP2 with the SSE in chromatin immunoprecipitation assays. p45 NF-E2 recruitment to the gamma-promoter is also lost, resulting in a reduction in RNA polymerase II and TBP binding and a fall in promoter transcriptional activity. This effect is specific, as enforced expression of a mutant form of p14 NF-E4, which fails to interact with CP2, also fails to repress gamma-gene expression in K562 cells. These findings provide one potential mechanism that could contribute to the autonomous silencing of the human gamma-genes in adult erythroid cells.

Indexed as

Erythroid Precursor CellsFetal BloodGene SilencingGlobinsHumansK562 CellsNF-E2 Transcription Factor, p45 SubunitProtein BindingProtein IsoformsResponse ElementsRNA Polymerase IITranscription FactorsTransduction, GeneticGlobinsNFE2 protein, humanNF-E2 Transcription Factor, p45 SubunitProtein IsoformsRNA Polymerase IItranscription factor NF-E4, humanTranscription Factors

Identifiers

PMID16263792
PMCPMC1895715
OpenAlexW2011891015

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.