Evidence map›Paper›PMID 21078662›Full record

ArticleThe Journal of biological chemistry2011

Histone deacetylase 9 activates gamma-globin gene expression in primary erythroid cells.

Shalini A Muralidhar, Valya Ramakrishnan, Inderdeep S Kalra, Wei Li, Betty S Pace

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 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
1.1field-weighted citation impact, top 22% 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, 27 citations in OpenAlex.

  1. Review
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  8. Omics Studies in Hemoglobinopathies.Molecular diagnosis & therapy · 2019
    Review
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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

5 authors at 2 institutions in 1 country.

Shalini A MuralidharDepartment of Molecular and Cell Biology, University of Texas at Dallas, Richardson, Texas 75080, USA.
Valya Ramakrishnan
Inderdeep S Kalra
Wei Li
Betty S Pace
The University of Texas at Dallas · USThe University of Texas Southwestern Medical Center · US

Funding

Mechanisms For p38 MAP Kinase DependentT Gene InductionR01HL069234 · NHLBI · UNIVERSITY OF TEXAS DALLAS · PI PACE, BETTY SUE · 2001 to 2017
$4.6M
NHLBI NIH HHS HL69234NHLBI NIH HHS R01 HL069234
6 · The paper itself

Abstract

Strategies to induce fetal hemoglobin (HbF) synthesis for the treatment of β-hemoglobinopathies probably involve protein modifications by histone deacetylases (HDACs) that mediate γ-globin gene regulation. However, the role of individual HDACs in globin gene expression is not very well understood; thus, the focus of our study was to identify HDACs involved in γ-globin activation. K562 erythroleukemia cells treated with the HbF inducers hemin, trichostatin A, and sodium butyrate had significantly reduced mRNA levels of HDAC9 and its splice variant histone deacetylase-related protein. Subsequently, HDAC9 gene knockdown produced dose-dependent γ-globin gene silencing over an 80-320 nm range. Enforced expression with the pTarget-HDAC9 vector produced a dose-dependent 2.5-fold increase in γ-globin mRNA (p < 0.05). Furthermore, ChIP assays showed HDAC9 binding in vivo in the upstream Gγ-globin gene promoter region. To determine the physiological relevance of these findings, human primary erythroid progenitors were treated with HDAC9 siRNA; we observed 40 and 60% γ-globin gene silencing in day 11 (early) and day 28 (late) progenitors. Moreover, enforced HDAC9 expression increased γ-globin mRNA levels by 2.5-fold with a simultaneous 7-fold increase in HbF. Collectively, these data support a positive role for HDAC9 in γ-globin gene regulation.

Indexed as

Gene Expression RegulationButyratesErythroid Cellsgamma-GlobinsGene Knockdown TechniquesGene SilencingHeminHistone Deacetylase InhibitorsHistone DeacetylasesHumansHydroxamic AcidsK562 CellsRepressor ProteinsResponse ElementsRNA, MessengerButyratesgamma-GlobinsHDAC9 protein, humanHeminHistone Deacetylase InhibitorsHistone DeacetylasesHydroxamic AcidsRepressor ProteinsRNA, Messengertrichostatin A

Identifiers

PMID21078662
PMCPMC3023528
OpenAlexW2023593100

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.