Evidence map›Paper›PMID 11459831›Full record

ArticleGenes & development2001

Down-regulation of TDT transcription in CD4(+)CD8(+) thymocytes by Ikaros proteins in direct competition with an Ets activator.

L A Trinh, R Ferrini, B S Cobb, A S Weinmann, K Hahm, P Ernst, I P Garraway, M Merkenschlager, S T Smale

Open access · diamondAbstract read
In one paragraph

Article in Genes & development, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
–field-weighted citation impact
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

46 citing papers in PubMed, 152 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. IKAROS in Acute Leukemia: A Positive Influencer or a Mean Hater?International journal of molecular sciences · 2023
    Review
  6. Article
  7. A Point Mutation in IKAROS ZF1 Causes a B Cell Deficiency in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2021
    Article
  8. Review
  9. Review
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. The Ikaros family of zinc-finger proteins.Acta pharmaceutica Sinica. B · 2016
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. 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.

L A TrinhHoward Hughes Medical Institute, Department of Microbiology, Immunology, and Molecular Genetics, and Molecular Biology Institute, University of California, Los Angeles, California 90095-1662, USA.
R Ferrini
B S Cobb
A S Weinmann
K Hahm
P Ernst
I P Garraway
M Merkenschlager
S T Smale
Hammersmith Hospital · GBUniversity of California, Los Angeles · USHoward Hughes Medical Institute · US

Funding

UCLA NIGMS T32 Program AssessmentT32GM007185 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI TORRES, JORGE · 1985 to 2020
$21.7M
UCLA Tumor Immunology Training ProgramT32CA009120 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI Steven M. Dubinett, MICHAEL A TEITELL · 1985 to 2026
$10.3M
REGULATION OF TDT EXPRESSION DURING LYMPHOPOIESISR01DK043726 · NIDDK · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI SMALE, STEPHEN T · 1996 to 2014
$4.2M
PREDOCTORAL TRAINING PROGRAM IN GENETIC MECHANISMS AT UCT32GM007104 · NIGMS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GOBER, JAMES W · 1985 to 2011
$3.6M
CHARACTERIZATION OF THE B ELEMENT IN TATA-LESS PROMOTERSF31HG000117 · NHGRI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GARRAWAY, ISLA · 1993 to 1997
–
GENETICS OF PARKINSON'S DISEASEZ01HG000117 · NHGRI · HUMAN GENOME RESEARCH · PI NUSSBAUM, ROBERT L · 1997 to 2005
–
Intramural NIH HHS Z01 HG000117NCI NIH HHS CA09120NCI NIH HHS T32 CA009120NHGRI NIH HHS F31 HG000117NIDDK NIH HHS R01 DK043726NIDDK NIH HHS R01 DK43726NIGMS NIH HHS GM07104NIGMS NIH HHS GM07185NIGMS NIH HHS T32 GM007104NIGMS NIH HHS T32 GM007185
6 · The paper itself

Abstract

Ikaros is a unique regulator of lymphopoiesis that associates with pericentromeric heterochromatin and has been implicated in heritable gene inactivation. Binding and competition experiments demonstrate that Ikaros dimers compete with an Ets activator for occupancy of the lymphocyte-specific TdT promoter. Mutations that selectively disrupt Ikaros binding to an integrated TdT promoter had no effect on promoter function in a CD4(+)CD8(+) thymocyte line. However, these mutations abolished down-regulation on differentiation, providing evidence that Ikaros plays a direct role in repression. Reduced access to restriction enzyme cleavage suggested that chromatin alterations accompany down-regulation. The Ikaros-dependent down-regulation event and the observed chromatin alterations appear to precede pericentromeric repositioning. Current models propose that the functions of Ikaros should be disrupted by a small isoform that retains the dimerization domain and lacks the DNA-binding domain. Surprisingly, in the CD4(+)CD8(+) thymocyte line, overexpression of a small Ikaros isoform had no effect on differentiation or on the pericentromeric targeting and DNA-binding properties of Ikaros. Rather, the small isoform assembled into multimeric complexes with DNA-bound Ikaros at the pericentromeric foci. The capacity for in vivo multimer formation suggests that interactions between Ikaros dimers bound to the TdT promoter and those bound to pericentromeric repeat sequences may contribute to the pericentromeric repositioning of the inactive gene.

Indexed as

DNA-Binding ProteinsBinding, CompetitiveBinding SitesCD4-Positive T-LymphocytesCD8-Positive T-LymphocytesCell DifferentiationCell LineCentromereChromatinDNA NucleotidylexotransferaseDown-RegulationEphrin-A2Ikaros Transcription FactorModels, GeneticPromoter Regions, GeneticProtein BindingChromatinDNA-Binding ProteinsDNA NucleotidylexotransferaseEphrin-A2Ikaros Transcription FactorTranscription Factors

Identifiers

PMID11459831
PMCPMC312741
OpenAlexW2114894459

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.