Evidence map›Paper›PMID 19460472›Full record

ArticleExperimental hematology2009

Complex developmental patterns of histone modifications associated with the human beta-globin switch in primary cells.

Mei Hsu, Christine A Richardson, Emmanuel Olivier, Caihong Qiu, Eric E Bouhassira, Christopher H Lowrey, Steven Fiering

Abstract read
In one paragraph

Article in Experimental hematology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.9field-weighted citation impact, top 27% 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

7 citing papers in PubMed, 13 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

7 authors at 2 institutions in 1 country.

Mei HsuDepartment of Microbiology and Immunology, and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03756, USA.
Christine A Richardson
Emmanuel Olivier
Caihong Qiu
Eric E Bouhassira
Christopher H Lowrey
Steven Fiering
Dartmouth College · USAlbert Einstein College of Medicine · US

Funding

Translational Engineering in Cancer (TEC)P30CA023108 · NCI · DARTMOUTH COLLEGE · PI Steven D Leach · 1985 to 2026
$91.3M
IMMUNOBIOLOGY OF MYELOID AND LYMPHOID CELLST32AI007363 · NIAID · DARTMOUTH COLLEGE · PI Claudia V Jakubzick · 1990 to 2026
$9.5M
Einstein Center for Human Embryonic Stem Cell ResearchP20GM075037 · NIGMS · ALBERT EINSTEIN COL OF MED YESHIVA UNIV · PI BOUHASSIRA, ERIC E · 2005 to 2007
$2.8M
Promoter Chromatin Structure in Fetal Globin SilencingR01HL073442 · NHLBI · DARTMOUTH COLLEGE · PI LOWREY, CHRISTOPHER H. · 2003 to 2010
$2.0M
Safe, Silencing-Resistant, Non-Oncogenic Globin Expression CassettesR01HL088467 · NHLBI · ALBERT EINSTEIN COLLEGE OF MEDICINE · PI BOUHASSIRA, ERIC E · 2007 to 2010
$1.8M
Gamma globin is silenced by chromatin changesR01HL073431 · NHLBI · DARTMOUTH COLLEGE · PI FIERING, STEVEN · 2003 to 2006
$1.3M
NCI NIH HHS P30 CA023108NHLBI NIH HHS HL088467NHLBI NIH HHS HL73431NHLBI NIH HHS HL73442NHLBI NIH HHS R01 HL073431NHLBI NIH HHS R01 HL073442NHLBI NIH HHS R01 HL088467NIAID NIH HHS T32 AI007363NIAID NIH HHS T32 AI07363NIGMS NIH HHS GM075037NIGMS NIH HHS P20 GM075037
6 · The paper itself

Abstract

objectiveThe regulation of the beta-globin switch remains undetermined, and understanding this mechanism has important benefits for clinical and basic science. Histone modifications regulate gene expression and this study determines the presence of three important histone modifications across the beta-globin locus in erythroblasts with different beta-like globin-expression profiles. Understanding the chromatin associated with weak gamma gene expression in bone marrow cells is an important objective, with the goal of ultimately inducing postnatal expression of weak gamma-globin to cure beta-hemoglobinopathies. MATERIALS AND

methodsThese studies use uncultured primary fetal and bone marrow erythroblasts and human embryonic stem cell-derived primitive-like erythroblasts. Chromatin immunoprecipitation with antibodies against modified histones reveals DNA associated with such histones. Precipitated DNA is quantitated by real-time polymerase chain reaction for 40 sites across the locus.

resultsDistribution of histone modifications differs at each developmental stage. The most highly expressed genes at each stage are embedded within large domains of modifications associated with expression (acetylated histone H3 [H3ac] and dimethyl lysine 4 of histone H3 [H3K4me2]). Moderately expressed genes have H3ac and H3K4me2 in the immediate area around the gene. Dimethyl lysine 9 of histone H3 (H3K9me2), a mark associated with gene suppression, is present at the epsilon and gamma genes in bone marrow cells, suggesting active suppression of these genes.

conclusionThis study reveals complex patterns of histone modifications associated with highly expressed, moderately expressed, and unexpressed genes. Activation of gamma postnatally will likely require extensive modification of the histones in a large domain around the gamma genes.

Indexed as

beta-GlobinsCells, CulturedChromatin ImmunoprecipitationHistonesHumansPolymerase Chain Reactionbeta-GlobinsHistones

Identifiers

PMID19460472
PMCPMC2748252
OpenAlexW1991144929

What OpenQuestion holds

Textmetadata
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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.