Evidence map›Paper›PMID 27152123›Full record

ArticleClinical epigenetics2016

Kaiso mediates human ICR1 methylation maintenance and H19 transcriptional fine regulation.

Florian Bohne, David Langer, Ursula Martiné, Claudia S Eider, Regina Cencic, Matthias Begemann, Miriam Elbracht, Luzie Bülow, Thomas Eggermann, Ulrich Zechner and 4 more

Open access · goldAbstract read
In one paragraph

Article in Clinical epigenetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.8field-weighted citation impact, top 13% 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

13 citing papers in PubMed, 29 citations in OpenAlex.

  1. Article
  2. Article
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  4. The remodeling of Z-DNA in the mammalian germ line.Biochemical Society transactions · 2022
    Article
  5. Article
  6. Kaiso Regulates DNA Methylation Homeostasis.International journal of molecular sciences · 2021
    Article
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  9. 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

14 authors at 6 institutions in 2 countries.

Florian Bohne *Centre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
David Langer *Centre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Ursula MartinéCentre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Claudia S EiderCentre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Regina CencicDepartment of Biochemistry and the Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6 Canada.
Matthias BegemannInstitute of Human Genetics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Miriam ElbrachtInstitute of Human Genetics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Luzie BülowInstitute of Human Genetics, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Thomas EggermannInstitute of Human Genetics, RWTH Aachen University, Pauwelsstr. 30, 52074 Aachen, Germany.
Ulrich ZechnerInstitute of Human Genetics, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Jerry PelletierDepartment of Biochemistry and the Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Quebec H3G 1Y6 Canada.
Bernhard Ulrich ZabelCentre for Paediatrics and Adolescent Medicine, University Medical Centre, Mathildenstr. 1, 79106 Freiburg, Germany.
Thorsten EnklaarCentre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Dirk PrawittCentre for Paediatrics and Adolescent Medicine, University Medical Centre, Langenbeckstr. 1, 55101 Mainz, Germany.
Johannes Gutenberg University Mainz · DERWTH Aachen University · DEGerman Center for Pediatric and Adolescent Rheumatology · DEMcGill University Health Centre · CAUniversity Medical Center Freiburg · DEUniversity Medical Center of the Johannes Gutenberg University Mainz · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenomic imprinting evolved in a common ancestor to marsupials and eutherian mammals and ensured the transcription of developmentally important genes from defined parental alleles. The regulation of imprinted genes is often mediated by differentially methylated imprinting control regions (ICRs) that are bound by different proteins in an allele-specific manner, thus forming unique chromatin loops regulating enhancer-promoter interactions. Factors that maintain the allele-specific methylation therefore are essential for the proper transcriptional regulation of imprinted genes. Binding of CCCTC-binding factor (CTCF) to the IGF2/H19-ICR1 is thought to be the key regulator of maternal ICR1 function. Disturbances of the allele-specific CTCF binding are causative for imprinting disorders like the Silver-Russell syndrome (SRS) or the Beckwith-Wiedemann syndrome (BWS), the latter one being associated with a dramatically increased risk to develop nephroblastomas.

methodsKaiso binding to the human ICR1 was detected and analyzed by chromatin immunoprecipitation (ChIP) and electrophoretic mobility shift assays (EMSA). The role of Kaiso-ICR1 binding on DNA methylation was tested by lentiviral Kaiso knockdown and CRISPR/Cas9 mediated editing of a Kaiso binding site.

resultsWe find that another protein, Kaiso (ZBTB33), characterized as binding to methylated CpG repeats as well as to unmethylated consensus sequences, specifically binds to the human ICR1 and its unmethylated Kaiso binding site (KBS) within the ICR1. Depletion of Kaiso transcription as well as deletion of the ICR1-KBS by CRISPR/Cas9 genome editing results in reduced methylation of the paternal ICR1. Additionally, Kaiso affects transcription of the lncRNA H19 and specifies a role for ICR1 in the transcriptional regulation of this imprinted gene.

conclusionsKaiso binding to unmethylated KBS in the human ICR1 is necessary for ICR1 methylation maintenance and affects transcription rates of the lncRNA H19.

Indexed as

DNA MethylationGenomic ImprintingTranscription, GeneticBinding SitesCells, CulturedFibroblastsHEK293 CellsHumansPromoter Regions, GeneticProtein BindingRNA, Long NoncodingTranscription FactorsH19 long non-coding RNARNA, Long NoncodingTranscription FactorsZBTB33 protein, human

Identifiers

PMID27152123
PMCPMC4857248
OpenAlexW2346557592

What OpenQuestion holds

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LicenceCC BY
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Registered trials

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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.