| Title |
Kaiso mediates human ICR1 methylation maintenance and H19 transcriptional fine regulation
|
|---|---|
| Published in |
Clinical Epigenetics, May 2016
|
| DOI | 10.1186/s13148-016-0215-4 |
| Pubmed ID | |
| Authors |
Florian Bohne, David Langer, Ursula Martiné, Claudia S. Eider, Regina Cencic, Matthias Begemann, Miriam Elbracht, Luzie Bülow, Thomas Eggermann, Ulrich Zechner, Jerry Pelletier, Bernhard Ulrich Zabel, Thorsten Enklaar, Dirk Prawitt |
| Abstract |
Genomic 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. Kaiso 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. We 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. Kaiso binding to unmethylated KBS in the human ICR1 is necessary for ICR1 methylation maintenance and affects transcription rates of the lncRNA H19. |
X Demographics
The data shown below were collected from the profiles of 10 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| United Kingdom | 3 | 30% |
| United States | 1 | 10% |
| France | 1 | 10% |
| Unknown | 5 | 50% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 6 | 60% |
| Scientists | 2 | 20% |
| Science communicators (journalists, bloggers, editors) | 1 | 10% |
| Practitioners (doctors, other healthcare professionals) | 1 | 10% |
Mendeley readers
The data shown below were compiled from readership statistics for 42 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Indonesia | 1 | 2% |
| Unknown | 41 | 98% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Researcher | 13 | 31% |
| Other | 5 | 12% |
| Student > Ph. D. Student | 4 | 10% |
| Professor > Associate Professor | 4 | 10% |
| Student > Master | 4 | 10% |
| Other | 7 | 17% |
| Unknown | 5 | 12% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 15 | 36% |
| Agricultural and Biological Sciences | 10 | 24% |
| Medicine and Dentistry | 5 | 12% |
| Neuroscience | 2 | 5% |
| Immunology and Microbiology | 1 | 2% |
| Other | 3 | 7% |
| Unknown | 6 | 14% |
Attention Score in Context
This research output has an Altmetric Attention Score of 6. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 May 2016.
All research outputs
#6,410,375
of 25,374,647 outputs
Outputs from Clinical Epigenetics
#437
of 1,436 outputs
Outputs of similar age
#85,178
of 312,451 outputs
Outputs of similar age from Clinical Epigenetics
#16
of 37 outputs
Altmetric has tracked 25,374,647 research outputs across all sources so far. This one has received more attention than most of these and is in the 74th percentile.
So far Altmetric has tracked 1,436 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 8.4. This one has gotten more attention than average, scoring higher than 69% of its peers.
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We're also able to compare this research output to 37 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 56% of its contemporaries.