Evidence map›Paper›PMID 21873977›Full record

ArticleThe EMBO journal2011

RUNX1 regulates the CD34 gene in haematopoietic stem cells by mediating interactions with a distal regulatory element.

Elena Levantini, Sanghoon Lee, Hanna S Radomska, Christopher J Hetherington, Meritxell Alberich-Jorda, Giovanni Amabile, Pu Zhang, David A Gonzalez, Junyan Zhang, Daniela S Basseres and 9 more

Open access · bronzeAbstract read
In one paragraph

Article in The EMBO journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
1.3field-weighted citation impact, top 19% 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

20 citing papers in PubMed, 29 citations in OpenAlex.

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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

19 authors at 11 institutions in 6 countries.

Elena LevantiniDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center, Center for Life Science, Boston, MA, USA. elevanti@bidmc.harvard.edu
Sanghoon Lee
Hanna S Radomska
Christopher J Hetherington
Meritxell Alberich-Jorda
Giovanni Amabile
Pu Zhang
David A Gonzalez
Junyan Zhang
Daniela S Basseres
Nicola K Wilson
Steffen Koschmieder
Gang Huang
Dong-Er Zhang
Alexander K Ebralidze
Constanze Bonifer
Yutaka Okuno
Bertie Gottgens
Daniel G Tenen
Harvard University · USBeth Israel Deaconess Medical Center · USUniversity of Cambridge · GBAugenstern · DECincinnati Children's Hospital Medical Center · USHarvard Stem Cell Institute · USInstitute of Biomedical Science · GBKumamoto University · JPNational University of Singapore · SGUniversity of California, San Diego · USUniversity of Leeds · GB

Funding

MOLECULAR BIOLOGY OF MYELOID DIFFERENTIATIONR01CA041456 · NCI · BETH ISRAEL DEACONESS MEDICAL CENTER · PI TENEN, DANIEL G · 1986 to 2010
$4.6M
Medical Research Council G0800784National Centre for the Replacement, Refinement and Reduction of Animals in Research G0900729/1NCI NIH HHS CA41456NCI NIH HHS R01 CA041456
6 · The paper itself

Abstract

The transcription factor RUNX1 is essential to establish the haematopoietic gene expression programme; however, the mechanism of how it activates transcription of haematopoietic stem cell (HSC) genes is still elusive. Here, we obtained novel insights into RUNX1 function by studying regulation of the human CD34 gene, which is expressed in HSCs. Using transgenic mice carrying human CD34 PAC constructs, we identified a novel downstream regulatory element (DRE), which is bound by RUNX1 and is necessary for human CD34 expression in long-term (LT)-HSCs. Conditional deletion of Runx1 in mice harbouring human CD34 promoter-DRE constructs abrogates human CD34 expression. We demonstrate by chromosome conformation capture assays in LT-HSCs that the DRE physically interacts with the human CD34 promoter. Targeted mutagenesis of RUNX binding sites leads to perturbation of this interaction and decreased human CD34 expression in LT-HSCs. Overall, our in vivo data provide novel evidence about the role of RUNX1 in mediating interactions between distal and proximal elements of the HSC gene CD34.

Indexed as

Gene Expression RegulationAnimalsAntigens, CD34Bone Marrow TransplantationChromatinCore Binding Factor Alpha 2 SubunitFetal BloodGenotypeHematopoietic Stem CellsHL-60 CellsHumansMiceMice, TransgenicModels, BiologicalRegulatory Sequences, Nucleic AcidAntigens, CD34ChromatinCore Binding Factor Alpha 2 SubunitRUNX1 protein, humanRunx1 protein, mouse

Identifiers

PMID21873977
PMCPMC3209778
OpenAlexW2158521756

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.