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Generation of isogenic models of Angelman syndrome and Prader-Willi syndrome in CRISPR/Cas9-engineered human embryonic stem cells.
PLoS One
November 2024
Department of Genetics and Genome Sciences, University of Connecticut School of Medicine, Farmington, CT, United States of America.
Angelman syndrome (AS) and Prader-Willi syndrome (PWS), two distinct neurodevelopmental disorders, result from loss of expression from imprinted genes in the chromosome 15q11-13 locus most commonly caused by a megabase-scale deletion on either the maternal or paternal allele, respectively. Each occurs at an approximate incidence of 1/15,000 to 1/30,000 live births and has a range of debilitating phenotypes. Patient-derived induced pluripotent stem cells (iPSCs) have been valuable tools to understand human-relevant gene regulation at this locus and have contributed to the development of therapeutic approaches for AS.
View Article and Find Full Text PDFAllele-specific DNA demethylation editing leads to stable upregulation of allele-specific gene expression.
iScience
October 2024
Institute of Biochemistry and Technical Biochemistry, University of Stuttgart, Allmandring 31, 70569 Stuttgart, Germany.
Epigenome editing is an emerging technology that allows to rewrite epigenome states and reprogram gene expression. Here, we have developed allele-specific DNA demethylation editing at gene promoters containing an SNP by sgRNA/dCas9 mediated recuitment of TET1. Maximal DNA demethylation (up to 90%) was observed 6 days after transient transfection of the epigenome editors and it was almost stable for 15 days.
View Article and Find Full Text PDFMethylome profile of medaka eggs and sperm.
Epigenetics
December 2024
Division of Biological Sciences, University of Missouri, Columbia, MO, USA.
Eggs and sperm are responsible for the continuation of generations. Following the epigenetic reprogramming of the embryo, core epigenetic information present in the sperm and eggs is transmitted to offspring somatic cells prior to the blastula stage, which specifically influences gene expression in the cells. Differences in the patterns of DNA methylation between the paternal and maternal genomes are critical to regulating allele-specific gene expression in the developing embryo, constituting the basis of genomic imprinting in mammals.
View Article and Find Full Text PDFDynamic patterns of gene expressional and regulatory variations in cotton heterosis.
Front Plant Sci
August 2024
Zhejiang Provincial Key Laboratory of Crop Genetic Resources, Institute of Crop Science, Plant Precision Breeding Academy, College of Agriculture and Biotechnology, Zhejiang University, Hangzhou, China.
Purpose: Although the application of heterosis has significantly increased crop yield over the past century, the mechanisms underlying this phenomenon still remain obscure. Here, we applied transcriptome sequencing to unravel the impacts of parental expression differences and transcriptomic reprogramming in cotton heterosis.
Methods: A high-quality transcriptomic atlas covering 15 developmental stages and tissues was constructed for XZM2, an elite hybrid of upland cotton ( L.
Imprinted DNA methylation of the H19 ICR is established and maintained in vivo in the absence of Kaiso.
Epigenetics Chromatin
June 2024
Institute of Life and Environmental Sciences, Life Science Center for Survival Dynamics, Tsukuba Advanced Research Alliance (TARA), University of Tsukuba, Tennoudai 1-1-1, Tsukuba, Ibaraki, 305-8577, Japan.
Background: Paternal allele-specific DNA methylation of the imprinting control region (H19 ICR) controls genomic imprinting at the Igf2/H19 locus. We previously demonstrated that the mouse H19 ICR transgene acquires imprinted DNA methylation in preimplantation mouse embryos. This activity is also present in the endogenous H19 ICR and protects it from genome-wide reprogramming after fertilization.
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