Evidence map›Paper›PMID 20940306›Full record

ArticleThe Journal of biological chemistry2010

Down-regulation of Myc is essential for terminal erythroid maturation.

Senthil Raja Jayapal, Kian Leong Lee, Peng Ji, Philipp Kaldis, Bing Lim, Harvey F Lodish

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.

0numbers the graph read from it
0cells of the map it votes in
60citing papers in PubMed
3.8field-weighted citation impact, top 7% 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

60 citing papers in PubMed, 82 citations in OpenAlex.

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  9. CDK4/6 inhibitor-induced bone marrow micronuclei might be caused by cell cycle arrest during erythropoiesis.Genes and environment : the official journal of the Japanese Environmental Mutagen Society · 2024
    Article
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  18. Altered CaCells · 2021
    Article
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  20. Review
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 6 institutions in 2 countries.

Senthil Raja JayapalComputation and Systems Biology, Singapore-Massachusetts Institute of Technology Alliance, 4 Engineering Drive 3, Singapore.
Kian Leong Lee
Peng Ji
Philipp Kaldis
Bing Lim
Harvey F Lodish
Beth Israel Deaconess Medical Center · USGenome Institute of Singapore · SGInstitute of Molecular and Cell Biology · SGMassachusetts Institute of Technology · USNational University of Singapore · SGWhitehead Institute for Biomedical Research · US

Funding

TRANSCRIPTION FACTOR GATA-1 IN TERMINAL ERYTHROID DEVELOPMENTP01HL032262 · NHLBI · CHILDREN'S HOSPITAL BOSTON · PI ORKIN, STUART H · 1985 to 2021
$38.9M
HEMATOPOIETIC SPECIFIC GENES IN STEM CELL DEVELOPMENTR01DK047636 · NIDDK · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LIM, BING · 1995 to 2008
$2.7M
CHARACTERIZATION OF A NEW MOUSE MODEL FOR LUPUSR01AI054973 · NIAID · BETH ISRAEL DEACONESS MEDICAL CENTER · PI LIM, BING · 2003 to 2007
$1.4M
NHLBI NIH HHS P01 HL032262NHLBI NIH HHS P01 HL32262NIAID NIH HHS AI54973NIAID NIH HHS R01 AI054973NIDDK NIH HHS DK047636NIDDK NIH HHS R01 DK047636
6 · The paper itself

Abstract

Terminal differentiation of mammalian erythroid progenitors involves 4-5 cell divisions and induction of many erythroid important genes followed by chromatin and nuclear condensation and enucleation. The protein levels of c-Myc (Myc) are reduced dramatically during late stage erythroid maturation, coinciding with cell cycle arrest in G(1) phase and enucleation, suggesting possible roles for c-Myc in either or both of these processes. Here we demonstrate that ectopic Myc expression affects terminal erythroid maturation in a dose-dependent manner. Expression of Myc at physiological levels did not affect erythroid differentiation or cell cycle shutdown but specifically blocked erythroid nuclear condensation and enucleation. Continued Myc expression prevented deacetylation of several lysine residues in histones H3 and H4 that are normally deacetylated during erythroid maturation. The histone acetyltransferase Gcn5 was up-regulated by Myc, and ectopic Gcn5 expression partially blocked enucleation and inhibited the late stage erythroid nuclear condensation and histone deacetylation. When overexpressed at levels higher than the physiological range, Myc blocked erythroid differentiation, and the cells continued to proliferate in cytokine-free, serum-containing culture medium with an early erythroblast morphology. Gene expression analysis demonstrated the dysregulation of erythropoietin signaling pathway and the up-regulation of several positive regulators of G(1)-S cell cycle checkpoint by supraphysiological levels of Myc. These results reveal an important dose-dependent function of Myc in regulating terminal maturation in mammalian erythroid cells.

Indexed as

AnimalsCell DifferentiationErythroblastsG1 PhaseGene DosageGene ExpressionHistonesMicep300-CBP-Associated Factorp300-CBP Transcription FactorsProto-Oncogene Proteins c-mycS PhaseHistonesMyc protein, mousep300-CBP-Associated Factorp300-CBP Transcription FactorsProto-Oncogene Proteins c-myc

Identifiers

PMID20940306
PMCPMC3001006
OpenAlexW1985470849

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.