Imprinting is an epigenetic modification leading to monoallelic expression of some genes, and disrupted imprinting is believed to be a barrier to human stem cell transplantation, based on studies that suggest that epigenetic marks are unstable in mouse embryonic germ (EG) and embryonic stem (ES) cells. However, stem cell imprinting has not previously been examined directly in humans. We found that three imprinted genes, TSSC5, H19, and SNRPN, show monoallelic expression in in vitro differentiated human EG-derived cells, and a fourth gene, IGF2, shows partially relaxed imprinting at a ratio from 4:1 to 5:1, comparable to that found in normal somatic cells. In addition, we found normal methylation of an imprinting control region (ICR) that regulates H19 and IGF2 imprinting, suggesting that imprinting may not be a significant epigenetic barrier to human EG cell transplantation. Finally, we were able to construct an in vitro mouse model of genomic imprinting, by generating EG cells from 8.5-day embryos of an interspecific cross, in which undifferentiated cells show biallelic expression and acquire preferential parental allele expression after differentiation. This model should allow experimental manipulation of epigenetic modifications of cultured EG cells that may not be possible in human stem cell studies.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC124986 | PMC |
| http://dx.doi.org/10.1073/pnas.152327599 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Genetic Heterogeneity in Four Probands Reveals , , and Related Neurodevelopmental Disorders.
Biomedicines
November 2024
Translational Genomics Laboratory, Department of Biosciences, COMSATS University, Islamabad 45550, Pakistan.
: Neurodevelopmental disorders of genetic etiology are a highly diverse set of congenital recurrent complications triggered by irregularities in the basic tenets of brain development. : We present whole exome sequencing analysis and expression characteristics of the probands from four unrelated Pakistani consanguineous families with facial dysmorphism, neurodevelopmental, ophthalmic, auditory, verbal, psychiatric, behavioral, dental, and skeletal manifestations otherwise unexplained by clinical spectrum. : Whole exome sequencing identifies a novel, bi-allelic, missense variant in the gene [NM_152419.
View Article and Find Full Text PDFCharacterization of Loss-of-Imprinting in Breast Cancer at the Cellular Level by Integrating Single-Cell Full-Length Transcriptome with Bulk RNA-Seq Data.
Biomolecules
December 2024
Department of Data Analysis and Mathematical Modelling, Faculty of Bioscience Engineering, Ghent University, 9000 Ghent, Belgium.
Genomic imprinting, the parent-of-origin-specific gene expression, plays a pivotal role in growth regulation and is often dysregulated in cancer. However, screening for imprinting is complicated by its cell-type specificity, which bulk RNA-seq cannot capture. On the other hand, large-scale single-cell RNA-seq (scRNA-seq) often lacks transcript-level detail and is cost-prohibitive.
View Article and Find Full Text PDFMonoallelic expression can govern penetrance of inborn errors of immunity.
Nature
January 2025
Columbia Center for Genetic Errors of Immunity, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Article Synopsis
- Inborn errors of immunity (IEIs) are genetic disorders that increase the risk of infections, autoimmunity, and other health issues, and often show incomplete penetrance despite being caused by single gene mutations.
- This study examines how autosomal random monoallelic expression (aRMAE)—where only one allele of a gene is actively expressed—contributes to the variability in disease outcomes among individuals within families with IEIs.
- The findings reveal that specific gene expression patterns related to aRMAE can influence clinical phenotypes, suggesting that understanding both genetic and expression variations is crucial for analyzing the impact of monogenic disorders.
Further evidence of biallelic NAV3 variants associated with recessive neurodevelopmental disorder with dysmorphism, developmental delay, intellectual disability, and behavioral abnormalities.
Hum Genet
December 2024
Department of Medical Genetics, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, Karnataka, India.
Neuron navigators (NAVs) are cytoskeleton-associated proteins well known for their role in axonal guidance, neuronal migration, and neurite growth necessary for neurodevelopment. Neuron navigator 3 (NAV3) is one of the three NAV proteins highly expressed in the embryonic and adult brain. However, the role of the NAV3 gene in human disease is not well-studied.
View Article and Find Full Text PDFMono-allelic epigenetic regulation of polycistronic transcription initiation by RNA polymerase II in .
mBio
December 2024
Department of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia, USA.
Unique for a eukaryote, protein-coding genes in trypanosomes are arranged in polycistronic transcription units (PTUs). This genome arrangement has led to a model where Pol II transcription of PTUs is unregulated and changes in gene expression are entirely post-transcriptional. is unable to infect humans because of its susceptibility to an innate immune complex, trypanosome lytic factor (TLF) in the circulation of humans.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!