Evidence map›Paper›PMID 19008453›Full record

ArticleBlood2009

An insulator with barrier-element activity promotes alpha-spectrin gene expression in erythroid cells.

Patrick G Gallagher, Douglas G Nilson, Laurie A Steiner, Yelena D Maksimova, Jolinta Y Lin, David M Bodine

Abstract read
In one paragraph

Article in Blood, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.1field-weighted citation impact, top 14% 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

13 citing papers in PubMed, 27 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

6 authors at 3 institutions in 1 country.

Patrick G GallagherDepartment of Pediatrics, Yale University School of Medicine, New Haven, CT 06520-8064, USA. patrick.gallagher@yale.edu
Douglas G Nilson
Laurie A Steiner
Yelena D Maksimova
Jolinta Y Lin
David M Bodine
Yale University · USNational Institutes of Health · USNational Human Genome Research Institute · US

Funding

Pediatric Scientist Development Program (PSDP) [K12]K12HD000850 · NICHD · YALE UNIVERSITY · PI Sallie R. Permar · 1987 to 2026
$44.1M
Red Cell BiologyZIAHG200339 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BODINE, DAVID M. · 2009 to 2022
$11.8M
MOLECULAR BIOLOGY OF HUMAN ERYTHROCYTE ALPHA-SPECTRINR01HL065448 · NHLBI · YALE UNIVERSITY · PI GALLAGHER, PATRICK G · 2000 to 2013
$4.4M
Gene Therapy for Hemoglobin DisordersZIAHG200340 · NHGRI · NATIONAL HUMAN GENOME RESEARCH INSTITUTE · PI BODINE, DAVID M. · 2009 to 2010
$868k
Intramural NIH HHSNHLBI NIH HHS HL65448NHLBI NIH HHS R01 HL065448NICHD NIH HHS HD000850NICHD NIH HHS K12 HD000850
6 · The paper itself

Abstract

Understanding mechanisms controlling expression of the alpha-spectrin gene is important for understanding erythropoiesis, membrane biogenesis, and spectrin-linked hemolytic anemia. We showed previously that a minimal alpha-spectrin promoter directed low levels of expression only in early erythroid development, indicating elements outside the promoter are required for expression in adult erythrocytes. Addition of noncoding exon 1' and intron 1' conferred a 10-fold increase in activity in reporter gene assays. In this report, we used a transgenic mouse model to show that addition of exon 1' and intron 1' to the alpha-spectrin promoter conferred tissue-specific expression of a linked (A)gamma-globin gene in erythroid cells at all developmental stages. Expression was nearly position-independent, as 21 of 23 lines expressed the transgene, and gamma-globin protein was present in 100% of erythrocytes, indicating uniform expression. Additional in vivo studies revealed that exon 1' functions as an insulator with barrier-element activity. Chromatin immunoprecipitation assays demonstrated that this region was occupied by the upstream stimulatory factors 1/2 (USF1/USF2), similar to the well-characterized chicken HS4 insulator. These data identify the first barrier element described in an erythrocyte membrane protein gene and indicate that exon 1' and intron 1' are excellent candidate regions for mutations in patients with spectrin-linked hemolytic anemia.

Indexed as

Anemia, HemolyticAnimalsErythroid CellsErythropoiesisExonsgamma-GlobinsGene Expression RegulationGenes, ReporterHumansIntronsMiceMice, TransgenicPromoter Regions, GeneticReticulocytesRNA, MessengerSpectringamma-GlobinsRNA, MessengerSpectrin

Identifiers

PMID19008453
PMCPMC2644083
OpenAlexW2071505900

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.