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Main conclusion: The information on core components in maize polycomb repressive complex 2 (PRC2) are updated at a genome-wide scale, and the protein–protein interaction networks of PRC2 components are further provided in maize. The evolutionarily conserved polycomb group (PcG) proteins form multi-subunits polycomb repressive complexes (PRCs) that repress gene expression via chromatin condensation. In Arabidopsis, three distinct PRC2s have been identified, each determining a specific developmental program with partly functional redundancy. However, the core components and biological functions of PRC2 in cereals remain obscure. Here, we updated the information on maize PRC2 components at a genome-wide scale. Maize PRC2 subunits are highly duplicated, with five MSI1, three E(z), two ESC and two Su(z)12 homologs. ZmFIE1 is preferentially expressed in the endosperm, whereas the remaining are broadly expressed in many tissues. ZmCLF/MEZ1 and ZmFIE1 are maternally expressed imprinted genes, in contrast to the paternal-dominantly expression of ZmFIE2 in the endosperm. In maize, E(z) members likely provide a scaffold for assembling PRC2 complexes, whereas Su(z)12 and p55/MSI1-like proteins together reinforce the complex; ESC members probably determine its specificity: FIE1-PRC2 regulates endosperm cell development, whereas FIE2-PRC2 controls other cell types. The duplicated Brassicaceae-specific MEA and FIS2 also directly interact with maize PRC2 members. Together, this study establishes a roadmap for protein–protein interactions of maize PRC2 components, providing new insights into their functions in the growth and development of cereals. [ABSTRACT FROM AUTHOR]

Regulation of gene expression without changing the DNA sequence is governed by epigenetic mechanisms. Epigenetic regulation is important for changing chromatin structure in response to environmental cues as well as maintaining chromatin structure after cell division. The epigenetic machinery can reversibly change chromatin function, allowing a wide variety of biological processes in multicellular organisms to be controlled. Epigenetic regulation ensures spatial and temporal accuracy of the expression of developmentally regulated genes. So far, few studies have focused on the relationship between epigenetic regulation and mammalian sex development, despite this being an interesting area of research. Sex development consists of three sequential stages: the undifferentiated stage, gonadal differentiation into testes or ovaries, and differentiation of internal and external genitalia. Some genetic studies have revealed that epigenetic regulation is required for proper gonadal differentiation in mice. Particularly, the epigenetic machinery plays an integral part in sex determination, which is the first step of gonadal differentiation. Mammalian sex determination is triggered by activation of the mammalian sex-determining gene, Sry , in a spatially and temporally accurate manner. Several studies have demonstrated that expression of Sry is controlled not only by specific transcription factors but also by the epigenetic machinery. Here, we focus on the epigenetic regulation of Sry expression. [ABSTRACT FROM AUTHOR]

Background: MicroRNAs (miRNAs) are short non-coding RNAs that are emerging as important post-transcriptional regulators of neuronal and synaptic development. The precise impact of miRNAs on presynaptic function and neurotransmission remains, however, poorly understood. Results: Here, we identify miR-27b—an abundant neuronal miRNA implicated in neurological disorders—as a global regulator of the presynaptic transcriptome. miR-27b influences the expression of three quarters of genes associated with presynaptic function in cortical neurons. Contrary to expectation, a large majority of these genes are up-regulated by miR-27b. This stimulatory effect is mediated by miR-27b-directed silencing of several transcriptional repressors that cooperate to suppress the presynaptic transcriptome. The strongest repressive activity appears to be mediated by Bmi1, a component of the polycomb repressive complex implicated in self-renewal of neural stem cells. miR-27b knockdown leads to reduced synaptogenesis and to a marked decrease in neural network activity, which is fully restored by RNAi-mediated silencing of Bmi1. Conclusions: We conclude that silencing of Bmi1 by miR-27b relieves repression of the presynaptic transcriptome and supports neurotransmission in cortical networks. These results expand the repressive activity of Bmi1 to genes involved in synaptic function and identify a unique post-transcriptional circuitry that stimulates expression of synaptic genes and promotes synapse differentiation. [ABSTRACT FROM AUTHOR]

The decline in the regenerative potential of tissues is one of the most evident characteristics of aging. Stem cell aging determines the aging phenotypes of tissues, and has thus been recognized as one of the hallmarks of mammalian aging. An emerging body of evidence supports an essential role for epigenetic controls in regulating cellular functions. Many epigenetic modifications become stabilized at a particular stage of development. However, epigenetic marks can also readily change over time. This 'epigenetic drift' contributes to changes in cellular phenotypes and when it takes place in adult stem cells, may play an important role in stem cell aging. Epigenetic alterations are now recognized as another hallmark of mammalian aging. This process depends on cell intrinsic and extrinsic factors, although the underlying molecular mechanisms remain largely unknown. Here, we review the current progress in the study of epigenetic changes regulating aging hematopoietic stem cells (HSCs). We particularly focus on the epigenome and its regulators in aging HSCs. [ABSTRACT FROM AUTHOR]

Highlights: [•] Nspc1 participates in maintaining P19 embryonal carcinoma cell’s pluripotency. [•] The epigenetics repressor Nspc1 positively regulates Oct4–Nanog–Sox2 axis. [•] Nspc1 directly binds and activates Oct4 promoter in a dose dependent manner. [•] The activation effect of Nspc1 is dependent on the RA response element. [ABSTRACT FROM AUTHOR]

Enhancer of zeste homolog 2 (EZH2) is a critical component of the polycomb-repressive complex 2 (PRC2), which is involved in gene silencing and histone H3 lysine 27 methylation. EZH2 has a master regulatory function in controlling such processes as stem cell differentiation, cell proliferation, early embryogenesis and X chromosome inactivation. Although benign epithelial cells express very low levels of EZH2, increased levels of EZH2 have been observed in aggressive solid tumors such as those of the prostate, breast and bladder. The mechanism by which EZH2 mediates tumor aggressiveness is unclear. Here, we demonstrate that EZH2 mediates transcriptional silencing of the tumor suppressor gene E-cadherin by trimethylation of H3 lysine 27. Histone deacetylase inhibitors can prevent EZH2-mediated repression of E-cadherin and attenuate cell invasion, suggesting a possible mechanism that may be useful for the development of therapeutic treatments. Taken together, these observations provide a novel mechanism of E-cadherin regulation and establish a functional link between dysregulation of EZH2 and repression of E-cadherin during cancer progression.Oncogene (2008) 27, 7274–7284; doi:10.1038/onc.2008.333; published online 22 September 2008 [ABSTRACT FROM AUTHOR]

Abnormal activation of the Wnt signaling pathway is found in 90% of colorectal cancers (CRCs). Secreted frizzled-related protein 4 (sFRP4) serves as an antagonist of the canonical Wnt signaling pathway. Epigenetic alterations, including changes in DNA methylation and histone methylation, may influence the expression of sFRP4. Polycomb group (PcG) proteins are epigenetic transcriptional repressors that selectively repress gene expression by forming polycomb repressive complexes (PRCs). Enhancer of zeste homolog 2 (EZH2), the core component of PRC2, is a histone-lysine N-methyltransferase that interacts with DNA methyltransferases. In the present study, the promoter DNA methylation status of sFRP4 in CRC cell lines was analyzed and the underlying mechanisms of action governing this modification was investigated. Firstly, the DNA methylation status of the sFRP4 promoter in CRC cell lines was assessed using methylation-specific PCR. Subsequently, the mRNA and protein levels of sFRP4 were measured using real-time qPCR and western blot analysis, respectively, to determine whether the DNA methylation status of the sFRP4 promoter is correlated with its transcriptional levels. To screen for important epigenetic modifiers that may regulate the promoter DNA methylation status of sFRP4, the expression levels of PcG proteins were examined by gene array analysis. ChIP-qPCR was performed to test whether the selected PcG proteins directly bind the promoter region of sFRP4. Finally, the downregulated PcG proteins EZH2, chromobox 7 (CBX7) and jumonji and AT-rich interaction domain containing 2 (JARID2) were identified and their association with sFRP4 expression levels and Wnt/β-catenin signaling pathway activity were investigated. The present study revealed that sFRP4 was hypermethylated in the promoter region and downregulated during the progression of the CRC cell lines from Dukes A to Dukes C. Expression levels of PcG proteins EZH2, CBX7 and JARID2 were upregulated and positively associated with the aberrantly activated Wnt signaling pathway in the CRC cell lines. EZH2, CBX7 and JARID2 were all enriched in the sFRP4 promoter region in CRC cells. EZH2 downregulation did not affect the promoter DNA methylation status of sFRP4 but increased its expression levels and decreased CRC cell proliferation. DNA methylation controls the expression of sFRP4. EZH2 regulates sFRP4 expression without affecting the DNA hypermethylation of the sFRP4 promoter and influences CRC cell proliferation and Wnt/β-catenin signaling pathway activities. [ABSTRACT FROM AUTHOR]