Shoring up DNA methylation and H3K27me3 domain demarcation at developmental genes

Mutual antagonism between DNA methylation and H3K27me3 histone methylation suggests a dynamic crosstalk between these epigenetic marks that could help ensure correct gene expression programmes. Work from Manzo et al (2017) now shows that an isoform of de novo DNA methyltransferase DNMT3A provides specificity in the system by depositing DNA methylation at adjacent "shores" of hypomethylated bivalent CpG islands (CGI) in mouse embryonic stem cells (mESCs). DNMT3A1-directed methylation appears to be instructive in maintaining the H3K27me3 profile at the hypomethylated bivalent CGI promoters of developmentally important genes.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Transcription News [amp ] Views Source Type: research

Related Links:

Researchers from the Wyss Institute at Harvard University have developed a new microfluidic lab-on-a-chip device that aims to more accurately model the complex biological properties of the blood-brain barrier (BBB). Their work, recently published in ...
Source: Medgadget - Category: Medical Devices Authors: Tags: Medicine Neurology Source Type: blogs
Publication date: Available online 15 June 2019Source: Seminars in Cancer BiologyAuthor(s): Michael Timaner, Kelvin Tsai, Yuval ShakedAbstractMesenchymal stem cells (MSCs) are multipotent stem cells derived from the mesoderm that give rise to several mesenchymal lineages, including osteoblasts, adipocytes, chondrocytes and myocytes. Their potent ability to home to tumors coupled with their differentiation potential and immunosuppressive function positions MSCs as key regulators of tumor fate. Here we review the existing knowledge on the involvement of MSCs in multiple tumor-promoting processes, including angiogenesis, epit...
Source: Seminars in Cancer Biology - Category: Cancer & Oncology Source Type: research
Multiprotein chromatin remodelling complexes show remarkable conservation of function amongst metazoans, even though components present in invertebrates are often found as multiple paralogous proteins in vertebrate complexes. In some cases, these paralogues specify distinct biochemical and/or functional activities in vertebrate cells. Here, we set out to define the biochemical and functional diversity encoded by one such group of proteins within the mammalian Nucleosome Remodelling and Deacetylation (NuRD) complex: Mta1, Mta2 and Mta3. We find that, in contrast to what has been described in somatic cells, MTA proteins are ...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Development & Differentiation, Stem Cells, Transcription Articles Source Type: research
Human pluripotent stem cells (hPSCs) are being increasingly utilized worldwide in investigating human development, and modeling and discovering therapies for a wide range of diseases as well as a source for cellular therapy. Yet, since the first isolation of human embryonic stem cells (hESCs) 20 years ago, followed by the successful reprogramming of human-induced pluripotent stem cells (hiPSCs) 10 years later, various studies shed light on abnormalities that sometimes accumulate in these cells in vitro. Whereas genetic aberrations are well documented, epigenetic alterations are not as thoroughly discussed. I...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Development & Differentiation, Stem Cells Review Source Type: research
Several autoimmune diseases including multiple sclerosis (MS) cause increased transcription of endogenous retroviruses (HERVs) normally repressed by heterochromatin. In parallel, HERV-derived sequences were reported to drive gene expression. Here, we have examined a possible link between promoter and enhancer divergent transcription and the production of HERV transcripts. We find that HERV-derived sequences are in general counter-selected at regulatory regions, a counter-selection that is strongest in brain tissues while very moderate in stem cells. By exposing T cells to the pesticide dieldrin, we further found that a ser...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Chromatin, Epigenetics, Genomics & Functional Genomics, Molecular Biology of Disease Articles Source Type: research
Bronchioalveolar stem cells (BASCs) are a potential source for lung regeneration, but direct in vivo evidence for a multipotential lineage contribution during homeostasis and disease is critically missing, since specific genetic labeling of BASCs has not been possible. We developed a novel cell tracing approach based on intein-mediated assembly of newly engineered split-effectors, allowing selective targeting of dual-marker expressing BASCs in the mouse lung. RNA sequencing of isolated BASCs demonstrates that BASCs show a distinct transcriptional profile, characterized by co-expression of bronchiolar and alveolar epit...
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Development & Differentiation, Immunology, Stem Cells Articles Source Type: research
Lung epithelial progenitor cell populations fulfill the needs of this complex facultative regenerative organ when exposed to insult and contribute to repair in either the airway or alveolar compartments. The presence of a cell that can populate both epithelia had been proposed previously but has remained elusive. In this issue, Salwig et al (2019) provide compelling, genetic evidence that supports a growing narrative—a rare population of bronchioalveolar stem cells (BASCs) that can contribute to both airway and alveolar epithelium in the distal murine lung.
Source: EMBO Journal - Category: Molecular Biology Authors: Tags: Development & Differentiation, Immunology, Stem Cells News [amp ] Views Source Type: research
AbstractMucopolysaccharidoses (MPS) are inborn errors of metabolism produced by a deficiency of one of the enzymes involved in the degradation of glycosaminoglycans (GAGs). Although taken separately, each type is rare. As a group, MPS are relatively frequent, with an overall estimated incidence of around 1 in 20,000 –25,000 births. Development of therapeutic options for MPS, including hematopoietic stem cell transplantation (HSCT) and enzyme replacement therapy (ERT), has modified the natural history of many MPS types. In spite of the improvement in some tissues and organs, significant challenges remain unsol ved, in...
Source: Drugs - Category: Drugs & Pharmacology Source Type: research
Conclusion:A certain concentration of magnesium ions plays an important role in new bone regeneration and reconstruction. It can be used as a simple and effective method to enhance the osteogenesis and angiogenesis of bioceramic scaffolds, and support the development of biomaterials and bone tissue engineering scaffolds.
Source: Tissue Engineering and Regenerative Medicine - Category: Biotechnology Source Type: research
Cancer Gene Therapy, Published online: 17 June 2019; doi:10.1038/s41417-019-0110-1Enhanced antitumor efficacy of an oncolytic adenovirus armed with an EGFR-targeted BiTE using menstrual blood-derived mesenchymal stem cells as carriers
Source: Cancer Gene Therapy - Category: Cancer & Oncology Authors: Source Type: research
More News: Genetics | Stem Cell Therapy | Stem Cells