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Oct4GiP Reporter Assay to Study Genes that Regulate Mouse Embryonic Stem Cell Maintenance and Self-renewal
Published on: May 30, 2012
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The long non-coding RNA Meg3 mediates imprinted gene expression during stem cell differentiation.
Sabina Farhadova1,2,3, Amani Ghousein1,2, François Charon4
1Institute of Molecular Genetics of Montpellier (IGMM), Centre National de Recherche Scientifique (CNRS), 34090 Montpellier, France.
Nucleic Acids Research
|April 13, 2024
Summary
The long non-coding RNA Meg3 is essential for repressing developmental genes Dlk1 and Rtl1 on the maternal chromosome. Meg3 also influences the three-dimensional genome structure, impacting gene regulation.
Area of Science:
- Genomics
- Epigenetics
- Developmental Biology
Background:
- The Dlk1-Dio3 locus is imprinted, with key developmental genes silenced on the maternal chromosome.
- The paternal allele expresses a polycistron including Meg3 long non-coding RNA (lncRNA), microRNAs, and snoRNAs.
Purpose of the Study:
- To investigate the role of Meg3 lncRNA in the cis-regulation of imprinted genes within the Dlk1-Dio3 domain.
- To determine if Meg3 lncRNA controls gene repression and influences chromatin structure.
Main Methods:
- Generation of mouse embryonic stem cells (mESCs) with reduced polycistron RNA levels and Rian knockout.
- CRISPR-mediated demethylation to achieve biallelic Meg3 expression.
- Capture Hi-C to analyze Topologically Associating Domain (TAD) organization.
Main Results:
- Meg3 lncRNA, but not Rian, is required for Dlk1 repression during ESC differentiation.
- Biallelic Meg3 expression led to repression of Dlk1 and loss of Rtl1 expression.
- Meg3 expression correlated with DNA hypomethylation, CTCF binding, and formation of a TAD linking Meg3 to Dlk1.
Conclusions:
- Meg3 lncRNA plays a crucial role in repressing Dlk1 and Rtl1 on the maternal chromosome.
- Meg3 is involved in establishing TAD structures that regulate gene expression within the Dlk1-Dio3 domain.
- Aberrant MEG3 expression may contribute to human imprinting disorders.
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