Evidence map›Paper›PMID 11085749›Full record

ArticleThe Journal of experimental medicine2000

Hematopoietic expression of HOXB4 is regulated in normal and leukemic stem cells through transcriptional activation of the HOXB4 promoter by upstream stimulating factor (USF)-1 and USF-2.

D M Giannola, W D Shlomchik, M Jegathesan, D Liebowitz, C S Abrams, T Kadesch, A Dancis, S G Emerson

Open access · bronzeAbstract read
In one paragraph

Article in The Journal of experimental medicine, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
1.1field-weighted citation impact, top 23% 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

22 citing papers in PubMed, 47 citations in OpenAlex.

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  15. NF-Ya activates multiple hematopoietic stem cell (HSC) regulatory genes and promotes HSC self-renewal.Proceedings of the National Academy of Sciences of the United States of America · 2005
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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

8 authors at 2 institutions in 1 country.

D M GiannolaDepartment of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
W D Shlomchik
M Jegathesan
D Liebowitz
C S Abrams
T Kadesch
A Dancis
S G Emerson
University of Pennsylvania · USYale University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The homeobox genes encode a family of transcription factors that regulate development and postnatal tissue homeostasis. Since HOXB4 plays a key role in regulating the balance between hematopoietic stem cell renewal and differentiation, we studied the molecular regulation of HOXB4 expression in human hematopoietic stem cells. HOXB4 expression in K562 cells is regulated at the level of transcription, and transient transfection defines primary HOXB4 regulatory sequences within a 99-bp 5' promoter. Culture of highly purified human CD34(+) bone marrow cells in thrombopoietin/Flt-3 ligand/stem cell factor induced HOXB4 3-10-fold, whereas culture in granulocyte/macrophage colony-stimulating factor, only increased HOXB4/luciferase expression 20-50%. Mutations within the HOXB4 promoter identified a potential E box binding site (HOX response element [HXRE]-2) as the most critical regulatory sequence, and yeast one hybrid assays evaluating bone marrow and K562 libraries for HXRE-2 interaction identified upstream stimulating factor (USF)-2 and micropthalmia transcription factor (MITF). Electrophoretic mobility shift assay with K562 extracts confirmed that these proteins, along with USF-1, bind to the HOXB4 promoter in vitro. Cotransfection assays in both K562 and CD34(+) cells showed that USF-1 and USF-2, but not MITF, induce the HOXB4 promoter in response to signals stimulating stem cell self-renewal, through activation of the mitogen-activated protein kinase pathway. Thus hematopoietic expression of the human HOXB4 gene is regulated by the binding of USF-1 and USF-2, and this process may be favored by cytokines promoting stem cell self-renewal versus differentiation.

Indexed as

DNA-Binding ProteinsHematopoietic Stem CellsBase SequenceBone Marrow CellsGenomic LibraryHomeodomain ProteinsHumansK562 CellsLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMitogen-Activated Protein KinasesMolecular Sequence DataNuclear ProteinsPromoter Regions, GeneticProtein Bindingras ProteinsSignal TransductionDNA-Binding ProteinsHomeodomain ProteinsHOXB4 protein, humanMitogen-Activated Protein KinasesNuclear Proteinsras ProteinsTranscription FactorsUpstream Stimulatory FactorsUSF1 protein, human

Identifiers

PMID11085749
PMCPMC2193192
OpenAlexW2093432029

What OpenQuestion holds

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LicenceCC BY-NC-SA
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.