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Inducible and Reversible Dominant-negative (DN) Protein Inhibition
Published on: January 7, 2019
Human PPP1R26P1 functions as cis-repressive element in mouse Rb1
Laura Steenpass1, Deniz Kanber, Michaela Hiber
1Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Plos One
|September 11, 2013
Summary
Human RB1 gene imprinting is linked to the PPP1R26P1 pseudogene. This pseudogene acts as a cis-repressive element, suppressing RB1 expression from the paternal allele via DNA methylation.
Area of Science:
- Genetics
- Epigenetics
- Molecular Biology
Background:
- The human retinoblastoma gene (RB1) exhibits imprinting, unlike its mouse counterpart.
- This imprinting is regulated by differential methylation of a CpG island (CpG85) within the PPP1R26P1 pseudogene in RB1 intron 2.
- CpG85 acts as a promoter for an alternative RB1 transcript, expressed only from the unmethylated paternal allele, potentially suppressing full-length RB1 expression.
Purpose of the Study:
- To investigate the role of the PPP1R26P1 pseudogene in regulating RB1 expression.
- To elucidate the mechanism of RB1 imprinting in humans.
Main Methods:
- Generation of an in vitro murine embryonic stem cell model by introducing human PPP1R26P1 into mouse Rb1.
- Next-generation bisulfite sequencing to analyze methylation status of CpG85 and CpG42.
- Assessment of RNA polymerase II binding and transcription at CpG85.
Main Results:
- Differential susceptibility of CpG85 and CpG42 to DNA methylation was observed, with median methylation gains of 4% and 18%, respectively.
- RNA polymerase II binding and transcription were detected at the unmethylated CpG85 within PPP1R26P1.
- Reduced expression of full-length Rb1 was observed from the targeted allele.
Conclusions:
- Human PPP1R26P1 functions as a cis-repressive element regulating RB1 expression.
- Retrotransposition of PPP1R26P1 into the human RB1 gene is linked to reduced paternal allele expression of RB1.
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