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1.
A. Shukla P. Chaurasia S. R. Bhaumik 《Cellular and molecular life sciences : CMLS》2009,66(8):1419-1433
Methylation of lysine residues of histones is associated with functionally distinct regions of chromatin, and, therefore,
is an important epigenetic mark. Over the past few years, several enzymes that catalyze this covalent modification on different
lysine residues of histones have been discovered. Intriguingly, histone lysine methylation has also been shown to be cross-regulated
by histone ubiquitination or the enzymes that catalyze this modification. These covalent modifications and their cross-talks
play important roles in regulation of gene expression, heterochromatin formation, genome stability, and cancer. Thus, there
has been a very rapid progress within past several years towards elucidating the molecular basis of histone lysine methylation
and ubiquitination, and their aberrations in human diseases. Here, we discuss these covalent modifications with their cross-regulation
and roles in controlling gene expression and stability.
Received 24 September 2008; received after revision 21 November 2008; accepted 28 November 2008 相似文献
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Kyoko Takahashi 《Cellular and molecular life sciences : CMLS》2014,71(6):1045-1054
Cellular information is inherited by daughter cells through epigenetic routes in addition to genetic routes. Epigenetics, which is primarily mediated by inheritable DNA methylation and histone post-translational modifications, involves changes in the chromatin structure important for regulating gene expression. It is widely known that epigenetic control of gene expression plays an essential role in cell differentiation processes in vertebrates. Furthermore, because epigenetic changes can occur reversibly depending on environmental factors in differentiated cells, they have recently attracted considerable attention as targets for disease prevention and treatment. These environmental factors include diet, exposure to bacteria or viruses, and air pollution, of which this review focuses on the influence of bacteria on epigenetic gene control in a host. Host-bacterial interactions not only occur upon pathogenic bacterial infection but also continuously exist between commensal bacteria and the host. These bacterial stimuli play an essential role in various biological responses involving external stimuli and in maintaining physiological homeostasis by altering epigenetic markers and machinery. 相似文献
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Complex diseases arise from a combination of heritable and environmental factors. The contribution made by environmental factors
may be mediated through epigenetics. Epigenetics is the study of changes in gene expression that occur without a change in
DNA sequence and are meiotically or mitotically heritable. Such changes in gene expression are achieved through the methylation
of DNA, the post-translational modifications of histone proteins, and RNA-based silencing. Epigenetics has been implicated
in complex diseases such as cancer, schizophrenia, bipolar disorder, autism and systemic lupus erythematosus. The prevalence
and severity of these diseases may be influenced by factors that affect the epigenotype, such as ageing, folate status, in vitro fertilization and our ancestors’ lifestyles. Although our understanding of the role played by epigenetics in complex diseases
remains in its infancy, it has already led to the development of novel diagnostic methods and treatments, which augurs well
for its future health benefits.
Received 6 December 2006; received after revision 29 January 2007; accepted 15 March 2007 相似文献
4.
Although all nucleated cells within a multicellular organism contain a complete copy of the genome, cell identity relies on
the expression of a specific subset of genes. Therefore, when cells divide they must not only copy their genome to their daughters,
but also ensure that the pattern of gene expression present before division is restored. While the carrier of this epigenetic
memory has been a topic of much research and debate, post-translational modifications of histone proteins have emerged in
the vanguard of candidates. In this paper we examine the mechanisms by which histone post-translational modifications are
propagated through DNA replication and cell division, and we critically examine the evidence that they can also act as vectors
of epigenetic memory. Finally, we consider ways in which epigenetic memory might be disrupted by interfering with the mechanisms
of DNA replication. 相似文献
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The aberrant epigenetic landscape of a cancer cell is characterized by global genomic hypomethylation, CpG island promoter
hypermethylation of tumor suppressor genes, and changes in histone modification patterns, as well as altered expression profiles
of chromatin-modifying enzymes. Recent advances in the field of epigenetics have revealed that microRNAs’ expression is also
under epigenetic regulation and that certain microRNAs control elements of the epigenetic machinery. The reversibility of
epigenetic marks catalyzed the development of epigenetic-altering drugs. However, a better understanding of the intertwined
relationship between genetics, epigenetics and microRNAs is necessary in order to resolve how gene expression aberrations
that contribute to tumorigenesis can be therapeutically corrected. 相似文献
7.
Endothelial nitric oxide synthase: insight into cell-specific gene regulation in the vascular endothelium 总被引:2,自引:0,他引:2
The vascular endothelium plays a crucial role in regulating normal blood vessel physiology. The gene products responsible
are commonly expressed exclusively, or preferentially, in this cell type. However, despite the importance of regulated gene
expression in the vascular endothelium, relatively little is known about the mechanisms that restrict endothelial-specific
gene expression to this cell type. While significant progress has been made towards understanding the regulation of endothelial
genes through cis/trans paradigms, it has become apparent that additional mechanisms must also be operative. For example,
chromatin-based mechanisms, including cell-specific DNA methylation patterns and post-translational histone modifications,
have recently been demonstrated to play important roles in the cell-specific expression of endothelial nitric oxide synthase
(eNOS). This review investigates the involvement of epigenetic regulatory mechanisms in vascular endothelial cell-specific
gene expression using eNOS as a prototypical model, and will address the possible contributions of these pathways to diseases
of the vasculature.
Received 13 September 2005; received after revision 13 October 2005; accepted 19 October 2005 相似文献
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Even though every cell in a multicellular organism contains the same genes, the differing spatiotemporal expression of these
genes determines the eventual phenotype of a cell. This means that each cell type contains a specific epigenetic program that
needs to be replicated through cell divisions, along with the genome, in order to maintain cell identity. The stable inheritance
of these programs throughout the cell cycle relies on several epigenetic mechanisms. In this review, DNA methylation and histone
methylation by specific histone lysine methyltransferases (KMT) and the Polycomb/Trithorax proteins are considered as the
primary mediators of epigenetic inheritance. In addition, non-coding RNAs and nuclear organization are implicated in the stable
transfer of epigenetic information. Although most epigenetic modifications are reversible in nature, they can be stably maintained
by self-recruitment of modifying protein complexes or maintenance of these complexes or structures through the cell cycle. 相似文献
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Juste Wesche Sarah Kühn Benedikt M. Kessler Maayan Salton Alexander Wolf 《Cellular and molecular life sciences : CMLS》2017,74(18):3305-3315
Arginine methylation of histones is one mechanism of epigenetic regulation in eukaryotic cells. Methylarginines can also be found in non-histone proteins involved in various different processes in a cell. An enzyme family of nine protein arginine methyltransferases catalyses the addition of methyl groups on arginines of histone and non-histone proteins, resulting in either mono- or dimethylated-arginine residues. The reversibility of histone modifications is an essential feature of epigenetic regulation to respond to changes in environmental factors, signalling events, or metabolic alterations. Prominent histone modifications like lysine acetylation and lysine methylation are reversible. Enzyme family pairs have been identified, with each pair of lysine acetyltransferases/deacetylases and lysine methyltransferases/demethylases operating complementarily to generate or erase lysine modifications. Several analyses also indicate a reversible nature of arginine methylation, but the enzymes facilitating direct removal of methyl moieties from arginine residues in proteins have been discussed controversially. Differing reports have been seen for initially characterized putative candidates, like peptidyl arginine deiminase 4 or Jumonji-domain containing protein 6. Here, we review the most recent cellular, biochemical, and mass spectrometry work on arginine methylation and its reversible nature with a special focus on putative arginine demethylases, including the enzyme superfamily of Fe(II) and 2-oxoglutarate-dependent oxygenases. 相似文献
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Melanija Posavec Gyula Timinszky Marcus Buschbeck 《Cellular and molecular life sciences : CMLS》2013,70(9):1509-1524
How metabolism and epigenetics are molecularly linked and regulate each other is poorly understood. In this review, we will discuss the role of direct metabolite-binding to chromatin components and modifiers as a possible regulatory mechanism. We will focus on globular macro domains, which are evolutionarily highly conserved protein folds that can recognize NAD+-derived metabolites. Macro domains are found in histone variants, histone modifiers, and a chromatin remodeler among other proteins. Here we summarize the macro domain-containing chromatin proteins and the enzymes that generate relevant metabolites. Focusing on the histone variant macroH2A, we further discuss possible implications of metabolite binding for chromatin function. 相似文献
16.
Jessica L. Slack Corey P. Causey Paul R. Thompson 《Cellular and molecular life sciences : CMLS》2011,68(4):709-720
The recent approvals of anticancer therapeutic agents targeting the histone deacetylases and DNA methyltransferases have highlighted
the important role that epigenetics plays in human diseases, and suggested that the factors controlling gene expression are
novel drug targets. Protein arginine deiminase 4 (PAD4) is one such target because its effects on gene expression parallel
those observed for the histone deacetylases. We demonstrated that F- and Cl-amidine, two potent PAD4 inhibitors, display micromolar
cytotoxic effects towards several cancerous cell lines (HL-60, MCF7 and HT-29); no effect was observed in noncancerous lines
(NIH 3T3 and HL-60 granulocytes). These compounds also induced the differentiation of HL-60 and HT29 cells. Finally, these
compounds synergistically potentiated the cell killing effects of doxorubicin. Taken together, these findings suggest PAD4
inhibition as a novel epigenetic approach for the treatment of cancer, and suggest that F- and Cl-amidine are candidate therapeutic
agents for this disease. 相似文献
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Marsh LM Pfefferle PI Pinkenburg O Renz H 《Cellular and molecular life sciences : CMLS》2011,68(11):1851-1862
Allergy and asthma are chronic inflammatory diseases which result from complex gene–environment interactions. Recent evidence
indicates the importance of prenatal and postnatal developmental processes in terms of maturation of balanced immune responses.
According to the current view, gene–environment interactions during a restricted time frame are responsible for programming
of the immune system in favor of allergic immune mechanisms later in life. The interaction between genes and environment is
complex and only partially understood; however, heritable epigenetic modifications including chemical additions in and alternative
packaging of the DNA have been shown to play a crucial role in this context. Novel data indicate that epigenetic mechanisms
contribute to the development of T-helper cell function. Environmental factors, including diesel exhaust particles (DEP),
vitamins and tobacco smoke, operate through such mechanisms. Furthermore, the role of environmental microbes provides another
and maybe even more important group of exogenous exposures which operates in this critical time frame. 相似文献
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Matrix metalloproteinase 9 (MMP-9) is one of the most studied enzymes in cancer. MMP-9 can cleave proteins of the extracellular matrix and a large number of receptors and growth factors. Accordingly, its expression must be tightly regulated to avoid excessive enzymatic activity, which is associated with disease progression. Although we know that epigenetic mechanisms play a central role in controlling mmp-9 gene expression, predicting how epigenetic drugs could be used to suppress mmp-9 gene expression is not trivial because epigenetic drugs also regulate the expression of key proteins that can tip the balance towards activation or suppression of MMP-9. Here, we review how our understanding of the biology and expression of MMP-9 could be exploited to augment clinical benefits, most notably in terms of the prevention and management of degenerative diseases and cancer. 相似文献
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DNA methylation is a stable but not irreversible epigenetic signal that silences gene expression. It has a variety of important functions in mammals, including control of gene expression, cellular differentiation and development, preservation of chromosomal integrity, parental imprinting and X-chromosome inactivation. In addition, it has been implicated in brain function and the development of the immune system. Somatic alterations in genomic methylation patterns contribute to the etiology of human cancers and ageing. It is tightly interwoven with the modification of histone tails and other epigenetic signals. Here we review our current understanding of the molecular enzymology of the mammalian DNA methyltransferases Dnmt1, Dnmt3a, Dnmt3b and Dnmt2 and the roles of the enzymes in the above-mentioned biological processes. 相似文献