Evidence map›Paper›PMID 20516218›Full record

ArticleMolecular and cellular biology2010

Gfi1 expression is controlled by five distinct regulatory regions spread over 100 kilobases, with Scl/Tal1, Gata2, PU.1, Erg, Meis1, and Runx1 acting as upstream regulators in early hematopoietic cells.

Nicola K Wilson, Richard T Timms, Sarah J Kinston, Yi-Han Cheng, S Helen Oram, Josette-Renee Landry, Joanne Mullender, Katrin Ottersbach, Berthold Gottgens

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In one paragraph

Article in Molecular and cellular biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.

0numbers the graph read from it
0cells of the map it votes in
45citing papers in PubMed
4.0field-weighted citation impact, top 6% 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

45 citing papers in PubMed, 65 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

9 authors at 1 institution in 1 country.

Nicola K WilsonUniversity of Cambridge, Department of Haematology, Cambridge Institute for Medical Research, Cambridge, United Kingdom.
Richard T Timms
Sarah J Kinston
Yi-Han Cheng
S Helen Oram
Josette-Renee Landry
Joanne Mullender
Katrin Ottersbach
Berthold Gottgens
University of Cambridge · GB

Funding

Cancer Research UKMedical Research Council G0800784National Centre for the Replacement, Refinement and Reduction of Animals in Research G0900729/1
6 · The paper itself

Abstract

The growth factor independence 1 (Gfi1) gene was originally discovered in the hematopoietic system, where it functions as a key regulator of stem cell homeostasis, as well as neutrophil and T-cell development. Outside the blood system, Gfi1 is essential for inner-ear hair and intestinal secretory cell differentiation. To understand the regulatory hierarchies within which Gfi1 operates to control these diverse biological functions, we used a combination of comparative genomics, locus-wide chromatin immunoprecipitation assays, functional validation in cell lines, and extensive transgenic mouse assays to identify and characterize the complete ensemble of Gfi1 regulatory elements. This concerted effort identified five distinct regulatory elements spread over 100kb each driving expression in transgenic mice to a subdomain of endogenous Gfi1. Detailed characterization of an enhancer 35 kb upstream of Gfi1 demonstrated activity in the dorsal aorta region and fetal liver in transgenic mice, which was bound by key stem cell transcription factors Scl/Tal1, PU.1/Sfpi1, Runx1, Erg, Meis1, and Gata2. Taken together, our results reveal the regulatory regions responsible for Gfi1 expression and importantly establish that Gfi1 expression at the sites of hematopoietic stem cell (HSC) emergence is controlled by key HSC regulators, thus integrating Gfi1 into the wider HSC regulatory networks.

Indexed as

AnimalsBasic Helix-Loop-Helix ProteinsCell DifferentiationCell LineChromatin ImmunoprecipitationHematopoiesisHematopoietic Stem CellsHematopoietic SystemHomeodomain ProteinsIntercellular Signaling Peptides and ProteinsMiceMice, TransgenicMyeloid Ecotropic Viral Integration Site 1 ProteinNeoplasm ProteinsProto-Oncogene ProteinsRegulatory Sequences, Nucleic AcidBasic Helix-Loop-Helix ProteinsHomeodomain ProteinsIntercellular Signaling Peptides and ProteinsMEIS1 protein, humanMeis1 protein, mouseMyeloid Ecotropic Viral Integration Site 1 ProteinNeoplasm ProteinsProto-Oncogene ProteinsTAL1 protein, humanT-Cell Acute Lymphocytic Leukemia Protein 1

Identifiers

PMID20516218
PMCPMC2916401
OpenAlexW2022859149

What OpenQuestion holds

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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.