Evidence map›Paper›PMID 24695324›Full record

ArticlePloS one2014

Krüppel like factor 4 promoter undergoes active demethylation during monocyte/macrophage differentiation.

Manjula Karpurapu, Ravi Ranjan, Jing Deng, Sangwoon Chung, Yong Gyu Lee, Lei Xiao, Teja Srinivas Nirujogi, Jeffrey R Jacobson, Gye Young Park, John W Christman

Open access · goldAbstract read
In one paragraph

Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.0field-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

24 citing papers in PubMed, 35 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

10 authors at 2 institutions in 1 country.

Manjula KarpurapuSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
Ravi RanjanSection of Pulmonary, Critical Care, Sleep and Allergy, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Jing DengSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
Sangwoon ChungSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
Yong Gyu LeeSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
Lei XiaoSection of Pulmonary, Critical Care, Sleep and Allergy, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Teja Srinivas NirujogiSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
Jeffrey R JacobsonInstitute for Personalized Respiratory Medicine, Department of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
Gye Young ParkSection of Pulmonary, Critical Care, Sleep and Allergy, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, United States of America.
John W ChristmanSection of Pulmonary, Allergy, Critical Care and Sleep Medicine, The Ohio State University Wexner Medical Center, Davis Heart and Lung Research Institute, Columbus, Ohio, United States of America.
The Ohio State University Wexner Medical Center · USUniversity of Illinois Chicago · US

Funding

Macrophage Gene Expression in Acute Lung InflammationR01HL075557 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHRISTMAN, JOHN W · 2004 to 2016
$4.8M
Pulmonary and Critical Care Post-Doctoral Research Training ProgramT32HL082547 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI FINN, PATRICIA W · 2007 to 2017
$2.7M
NADPH OXIDASE REGULATION OF THE MACROPHAGE INFLAMMATORY PHENOTYPE IN SEPSISR01HL103643 · NHLBI · UNIVERSITY OF ILLINOIS AT CHICAGO · PI CHRISTMAN, JOHN W · 2010 to 2013
$1.5M
BLRD VA I01 BX000108NHLBI NIH HHS HL 103643NHLBI NIH HHS R01 HL075557NHLBI NIH HHS R01 HL103643NHLBI NIH HHS T32 HL082547
6 · The paper itself

Abstract

The role of different lineage specific transcription factors in directing hematopoietic cell fate towards myeloid lineage is well established but the status of epigenetic modifications has not been defined during this important developmental process. We used non proliferating, PU.1 inducible myeloid progenitor cells and differentiating bone marrow derived macrophages to study the PU.1 dependent KLF4 transcriptional regulation and its promoter demethylation during monocyte/macrophage differentiation. Expression of KLF4 was regulated by active demethylation of its promoter and PU.1 specifically bound to KLF4 promoter oligo harboring the PU.1 consensus sequence. Methylation specific quantitative PCR and Bisulfite sequencing indicated demethylation of CpG residues most proximal to the transcription start site of KLF4 promoter. Cloned KLF4 promoter in pGL3 Luciferase and CpG free pcpgf-bas vectors showed accentuated reporter activity when co-transfected with the PU.1 expression vector. In vitro methylation of both KLF4 promoter oligo and cloned KLF4 promoter vectors showed attenuated in vitro DNA binding activity and Luciferase/mouse Alkaline phosphotase reporter activity indicating the negative influence of KLF4 promoter methylation on PU.1 binding. The Cytosine deaminase, Activation Induced Cytidine Deaminase (AICDA) was found to be critical for KLF4 promoter demethylation. More importantly, knock down of AICDA resulted in blockade of KLF4 promoter demethylation, decreased F4/80 expression and other phenotypic characters of macrophage differentiation. Our data proves that AICDA mediated active demethylation of the KLF4 promoter is necessary for transcriptional regulation of KLF4 by PU.1 during monocyte/macrophage differentiation.

Indexed as

AnimalsBinding SitesCell DifferentiationCytidine DeaminaseGene Expression RegulationKruppel-Like Factor 4Kruppel-Like Transcription FactorsMacrophagesMethylationMiceMice, Inbred C57BLMonocytesMyeloid Progenitor CellsPromoter Regions, GeneticTranscription, GeneticTranscription Initiation SiteCytidine DeaminaseKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription Factors

Identifiers

PMID24695324
PMCPMC3973678
OpenAlexW2035352210

What OpenQuestion holds

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LicenceCC BY
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.