Evidence map›Paper›PMID 31009133›Full record

ArticleJournal of cellular biochemistry2019

SP1 regulates KLF4 via SP1 binding motif governed by DNA methylation during odontoblastic differentiation of human dental pulp cells.

Zheyi Sun, Shuaitong Yu, Shuo Chen, Huan Liu, Zhi Chen

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of cellular biochemistry, 2019. 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
1.6field-weighted citation impact, top 16% 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, 43 citations in OpenAlex.

  1. [Research Advances on Mechanisms and Interventions of DNA Methylation-Regulated Aging-Related Imbalance in Bone Metabolism].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2026
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  18. LH-induced Transcriptional Regulation ofInternational journal of molecular sciences · 2020
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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 2 countries.

Zheyi SunState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Shuaitong YuState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Shuo ChenDepartment of Developmental Dentistry, University of Texas Health Science Center, San Antonio, Texas.
Huan LiuState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.
Zhi ChenState Key Laboratory Breeding Base of Basic Science of Stomatology (Hubei-MOST) and Key Laboratory for Oral Biomedicine of Ministry of Education (KLOBM), School and Hospital of Stomatology, Wuhan University, Wuhan, China.ORCID 0000-0003-2095-1324
Wuhan University · CNThe University of Texas Health Science Center at San Antonio · US

Funding

DSPP signaling in dentinogenesisR01DE019802 · NIDCR · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Shuo Chen · 2009 to 2026
$3.4M
NIDCR NIH HHS R01 DE019802
6 · The paper itself

Abstract

objectiveDNA methylation is a critical epigenetic modulation in regulating gene expression in cell differentiation process, however, its detailed molecular mechanism during odontoblastic differentiation remains elusive. We aimed to study the global effect of DNA methylation on odontoblastic differentiation and how DNA methylation affects the transactivation of transcription factor (TF) on its target gene.

methodsDNA methyltransferase (DNMTs) inhibition assay and following odontoblastic differentiation assay were performed to evaluate the effect of DNA methylation inhibition on odontoblastic differentiation. Promoter DNA methylation microarray and motif enrichment assay were performed to predict the most DNA-methylation-affected TF motifs during odontoblastic differentiation. The enriched target sites and motifs were further analyzed by methylation-specific polymerase chain reaction (MS-PCR) and sequencing. The functional target sites were validated in vitro with Luciferase assay. The regulatory effect of DNA methylation on the enriched target sites in primary human dental pulp cells and motifs were confirmed by in vitro methylation assay.

resultsInhibition of DNMTs in preodontoblast cells increased the expression level of Klf4 as well as marker genes of odontoblastic differentiation including Dmp1 and Dspp, and enhanced the efficiency of odontoblastic differentiation. SP1/KLF4 binding motifs were found to be highly enriched in the promoter regions and showed demethylation during odontoblastic differentiation. Mutation of SP1 binding site at -75 within KLF4's promoter region significantly decreased the luciferase activity. The in vitro methylation of KLF4's promoter decreased the transactivation of SP1 on KLF4.

conclusionWe confirmed that SP1 regulates KLF4 through binding site lying in a CpG island in KLF4's promoter region which demethylated during odontoblastic differentiation thus enhancing the efficiency of SP1's binding and transcriptional regulation on KLF4.

Indexed as

Cell DifferentiationDNA MethylationGene Expression RegulationAnimalsApoptosisCell ProliferationCells, CulturedCpG IslandsDental PulpDNA (Cytosine-5-)-Methyltransferase 1HumansKruppel-Like Factor 4Kruppel-Like Transcription FactorsMiceOdontoblastsPromoter Regions, GeneticDNA (Cytosine-5-)-Methyltransferase 1DNMT1 protein, humanKLF4 protein, humanKlf4 protein, mouseKruppel-Like Factor 4Kruppel-Like Transcription FactorsSP1 protein, humanSp1 Transcription FactorDNA methylationhuman dental pulp cellsKlf4odontoblastic differentiationSP1

Identifiers

PMID31009133
PMCPMC8895433
OpenAlexW2941369662

What OpenQuestion holds

Textmetadata
LicenceTDM
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.