PRC2 during vertebrate organogenesis: a complex in transition

During organogenesis, tissues expand in size and eventually acquire consistent ratios of cells with dazzling diversity in morphology and function. During this process progenitor cells exit the cell cycle and execute differentiation programs through extensive genetic reprogramming that involves the silencing of proliferation genes and the activation of differentiation genes in a step-wise temporal manner. Recent years have witnessed expansion in our understanding of the epigenetic mechanisms that contribute to cellular differentiation and maturation during organ development, as this is a crucial step toward advancing regenerative therapy research for many intractable disorders. Among such epigenetic programs, the developmental roles of the polycomb repressive complex 2 (PRC2), a chromatin remodeling complex that mediates silencing of gene expression, have been under intensive examination. This review summarizes recent findings of how PRC2 functions to regulate the transition from proliferation to differentiation during organogenesis and discusses some aspects of the remaining questions associated with its regulation and mechanisms of action.     

Epigenetic modifications of histones during osteoblast differentiation

In bone biology, epigenetics plays a key role in mesenchymal stem cells' (MSCs) commitment towards osteoblasts. It involves gene regulatory mechanisms governed by chromatin modulators. Predominant epigenetic mechanisms for efficient osteogenic differentiation include DNA methylation, histone modifications, and non-coding RNAs. Among these mechanisms, histone modifications critically contribute to altering chromatin configuration. Histone based epigenetic mechanisms are an essential mediator of gene expression during osteoblast differentiation as it directs the bivalency of the genome. Investigating the importance of histone modifications in osteogenesis may lead to the development of epigenetic-based remedies for genetic disorders of bone. Hence, in this review, we have highlighted the importance of epigenetic modifications such as post-translational modifications of histones, including methylation, acetylation, phosphorylation, ubiquitination, and their role in the activation or suppression of gene expression during osteoblast differentiation. Further, we have emphasized the future advancements in the field of epigenetics towards orthopaedical therapeutics.     

Histone deacetylase activity is required for embryonic stem cell differentiation

Mammalian development requires commitment of cells to restricted lineages, which requires epigenetic regulation of chromatin structure. Epigenetic modifications were examined during in vitro differentiation of murine embryonic stem (ES) cells. Global histone acetylation, a euchromatin marker, declines dramatically within 1 day of differentiation induction and partially rebounds by day 2. Histone H3-Lys9 methylation, a heterochromatin marker, increases during in vitro differentiation. Conversely, the euchromatin marker H3-Lys4 methylation transiently decreases, then increases to undifferentiated levels by day 4, and decreases by day 6. Global cytosine methylation, another heterochromatin marker, increases slightly during ES cell differentiation. Chromatin structure of the Oct4 and Brachyury gene promoters is modulated in concert with their pattern of expression during ES cell differentiation. Importantly, prevention of global histone deacetylation by treatment with trichostatin A prevents ES cell differentiation. Hence, ES cells undergo functionally important global and gene-specific remodeling of chromatin structure during in vitro differentiation. genesis 38:32-38, 2004.     

Glial epigenetics in neuroinflammation and neurodegeneration

Epigenetic regulation shapes the differentiation and response to stimuli of all tissues and cells beyond what genetics would dictate. Epigenetic regulation acts through covalent modifications of DNA and histones while leaving the nucleotide code intact. However, these chromatin modifications are known to be vital components of the regulation of cell fate and response. With regards to the central nervous system (CNS), little is known about how epigenetic regulation shapes the function of neural cell types. The focus of research so far has been on epigenetic regulation of neuronal function and the role of epigenetics in tumorigenesis. However, the glial cell compartment, which makes up 90 % of all CNS cells, has so far received scant attention as to how epigenetics shape their differentiation and function. Here, we highlight current knowledge about epigenetic changes in glial cells occurring during CNS injury, neuroinflammatory conditions and neurodegenerative disease. This review offers an overview of the current understanding of epigenetic regulation in glial cells in CNS disease.     

Chromatin and Arabidopsis root development

During development cells transit through different states as they pass from stem cell to terminally differentiated cell. There is evidence that the transition from one state to another can be accompanied by changes in epigenetic state of genes, which is embodied in chromatin state. Here we give an overview of the changes in chromatin that accompany the regulation of expression and review the evidence for the involvement of such changes during epidermal root development and discuss the roles that these changes play in the differentiation of the cell types involved.     

Epigenomics of cancer – emerging new concepts

The complexity of the mammalian genome is regulated by heritable epigenetic mechanisms, which provide the basis for differentiation, development and cellular homeostasis. These mechanisms act on the level of chromatin, by modifying DNA, histone proteins and nucleosome density/composition. During the last decade it became clear that cancer is defined by a variety of epigenetic changes, which occur in early stages of disease and parallel genetic mutations. With the advent of new technologies we are just starting to unravel the cancer epigenome and latest mechanistic findings provide the first clue as to how altered epigenetic patterns might occur in different cancers. Here we review latest findings on chromatin related mechanisms and hypothesize how their impairment might contribute to the altered epigenome of cancer cells.     

Chromatin and Arabidopsis root development

During development cells transit through different states as they pass from stem cell to terminally differentiated cell. There is evidence that the transition from one state to another can be accompanied by changes in epigenetic state of genes, which is embodied in chromatin state. Here we give an overview of the changes in chromatin that accompany the regulation of expression and review the evidence for the involvement of such changes during epidermal root development and discuss the roles that these changes play in the differentiation of the cell types involved.