Evidence map›Paper›PMID 12832463›Full record

ArticleMolecular and cellular biology2003

Variegated expression from the murine band 3 (AE1) promoter in transgenic mice is associated with mRNA transcript initiation at upstream start sites and can be suppressed by the addition of the chicken beta-globin 5' HS4 insulator element.

Tiffany F Frazar, Jessica L Weisbein, Stacie M Anderson, Amanda P Cline, Lisa J Garrett, Gary Felsenfeld, Patrick G Gallagher, David M Bodine

Open access · greenAbstract read
In one paragraph

Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
1.8field-weighted citation impact, top 15% 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

8 citing papers in PubMed, 24 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

8 authors at 4 institutions in 2 countries.

Tiffany F FrazarHematopoiesis Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, Bethesda, Maryland 20892, USA.
Jessica L Weisbein
Stacie M Anderson
Amanda P Cline
Lisa J Garrett
Gary Felsenfeld
Patrick G Gallagher
David M Bodine
Laboratory of Molecular Genetics · PLNational Human Genome Research Institute · USNational Institute of Diabetes and Digestive and Kidney Diseases · USNational Institutes of Health · US

Funding

MOLECULAR BIOLOGY OF HUMAN ERYTHROCYTE ALPHA-SPECTRINR01HL065448 · NHLBI · YALE UNIVERSITY · PI GALLAGHER, PATRICK G · 2000 to 2013
$4.4M
HEMATOPOIETIC STEM CELL BIOLOGYZ01HG000083 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BODINE, DAVID M. · 1996 to 2008
$1.1M
CHROMATIN STRUCTURE AND FUNCTIONZ01DK034001 · NIDDK · DIABETES, DIGESTIVE, KIDNEY DISEASES · PI FELSENFELD, GARY · 1986 to 2006
–
Inproving gene transfer to provide intracellular immunizZ01HG000197 · NHGRI · HUMAN GENOME RESEARCH · PI BODINE, DAVID M. · 2001 to 2006
–
NHLBI NIH HHS HL65448NHLBI NIH HHS R01 HL065448
6 · The paper itself

Abstract

The anion exchanger protein 1 (AE1; band 3) is an abundant erythrocyte transmembrane protein that regulates chloride-bicarbonate exchange and provides an attachment site for the erythrocyte membrane skeleton on the cytoplasmic domain. We analyzed the function of the erythroid AE1 gene promoter by using run-on transcription, RNase protection, transient transfection, and transgenic mouse assays. AE1 mRNA was transcribed at a higher level and maintained at a higher steady-state level than either ankyrin or beta-spectrin in mouse fetal liver cells. When linked to a human gamma-globin gene, two different AE1 promoters directed erythroid-specific expression of gamma-globin mRNA in 18 of 18 lines of transgenic mice. However, variegated expression of gamma-globin was observed in 14 of 18 lines. While there was a significant correlation between transgene copy number and the amount of gamma-globin mRNA in all 18 lines, the transgene mRNAs initiated upstream of the start site of the endogenous AE1 mRNA. Addition of the insulator element from 5'HS4 of the chicken beta-globin cluster to the AE1/gamma-globin transgene allowed position-independent, copy-number-dependent expression at levels similar to the AE1 transcription rate in six of six lines of transgenic mice. The mRNA from the insulated AE1/gamma-globin transgene mapped to the start site of the endogenous AE1 mRNA, and gamma-globin protein was expressed in 100% of erythrocytes in all lines. We conclude that the chicken beta-globin 5'HS4 element is necessary for full function of the AE1 promoter and that position effect variegation is associated with RNA transcription from the upstream start sites.

Indexed as

Insulator ElementsTranscription, GeneticTranscription Initiation SiteAnimalsAnion Exchange Protein 1, ErythrocyteBeta-GlobulinsCell NucleusChickensErythrocyte MembraneGene Expression RegulationGlobinsHumansLiverMiceMice, TransgenicPromoter Regions, GeneticAnion Exchange Protein 1, ErythrocyteBeta-GlobulinsGlobinsRNA, Messenger

Identifiers

PMID12832463
PMCPMC162203
OpenAlexW2158931590

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.