Histochemistry,Cytochemistry and Epigenetics

Over the past few decades, many researchers have individually identified tumor-related genes, and have accumulated information on their basic research in a database. With the development of technology that can comprehensively test the expression status within a short time, oncogene panel testing has become attainable. On the other hand, changes in gene expression that do not depend on changes in base sequences, that is, epigenetics, or more comprehensively, epigenomes, are also highly involved in the development and progression of disease. Oncogene panel tests tend to focus on DNA base mutations such as point mutations, deletions, duplications, and chimera formation. Elucidation leads to correct interpretation of diseases and treatment choices, and we are in an era where integrated understanding of the genome and epigenome is indispensable. In this review, we make every effort to cover a wide range of knowledge, including data on histone protein modification, non-coding (nc)RNA and DNA methylation, and recent application trials for demonstrating epigenetic alterations in histologic and cytologic specimens. We hope this review will help marshal the knowledge accumulated by researchers involved in genomic and epigenomic studies.     

Secondary Metabolite Gene Regulation in Mycotoxigenic Fusarium Species: A Focus on Chromatin

Fusarium is a species-rich group of mycotoxigenic plant pathogens that ranks as one of the most economically important fungal genera in the world. During growth and infection, they are able to produce a vast spectrum of low-molecular-weight compounds, so-called secondary metabolites (SMs). SMs often comprise toxic compounds (i.e., mycotoxins) that contaminate precious food and feed sources and cause adverse health effects in humans and livestock. In this context, understanding the regulation of their biosynthesis is crucial for the development of cropping strategies that aim at minimizing mycotoxin contamination in the field. Nevertheless, currently, only a fraction of SMs have been identified, and even fewer are considered for regular monitoring by regulatory authorities. Limitations to exploit their full chemical potential arise from the fact that the genes involved in their biosynthesis are often silent under standard laboratory conditions and only induced upon specific stimuli mimicking natural conditions in which biosynthesis of the respective SM becomes advantageous for the producer. This implies a complex regulatory network. Several components of these gene networks have been studied in the past, thereby greatly advancing the understanding of SM gene regulation and mycotoxin biosynthesis in general. This review aims at summarizing the latest advances in SM research in these notorious plant pathogens with a focus on chromatin structure.     

表遗传学与肿瘤

通常认为遗传学上的基因突变是肿瘤发病机制中的关键事件,尤其是抑癌基因的体细胞突变与肿瘤的发生有着密切的关系。但是,近年来随着对肿瘤认识的深入,人们发现DNA序列以外的调控机制异常在肿瘤的发生、发展过程中更为普遍,也更为重要。这种调控机制被称为表观遗传学（Epigenetics）,研究没有DNA序列变化的,可遗传的表达改变。例如基因启动子区CpG岛甲基化模式的异常与许多肿瘤的发生有着密切的关系。除了DNA甲基化调控形式外,表观遗传学还包括基因组印迹、染色质组蛋白修饰、隔离蛋白以及非编码RNA（包括microRNA）等DNA序列本身以外的各种调控方式。本文将就表观遗传学调控机制与肿瘤发生的关系作一简要综述。     

曲古霉素A体外诱导膀胱癌细胞凋亡及细胞周期阻滞的机制探讨

目的:观察组蛋白去乙酰化酶(HDAC)抑制剂曲古霉素A(TSA)对体外培养膀胱癌细胞生长情况及相关基因表达的影响,并探讨其可能的作用机制.方法:MTT法检测不同浓度(0.05、0.1、0.2、0.4、0.8 μmol/L)的TSA对人膀胱癌T24细胞生长的影响.透射电镜观察TSA(0.4 μmol/L) 诱导后膀胱癌细胞的形态学变化;流式细胞术检测处理后膀胱癌细胞周期分布及凋亡率的变化;Western 印迹法检测处理后膀胱癌细胞组蛋白乙酰化水平的变化;FQ-PCR检测处理后膀胱癌细胞p21CIP1/WAF1、cyclin A和cyclin E mRNA的表达.结果:TSA体外能明显抑制T24细胞生长,且抑制作用呈明显的剂量、时间依赖性.TSA(0.4 μmol/L)诱导后,透射电镜下可见大量具有凋亡形态特征的T24细胞;流式细胞术检测示细胞阻滞于G0/G1期,并且出现典型的亚二倍体(Sub-G1)峰;TSA可明显提高组蛋白乙酰化水平,并诱导p21CIP1/WAF1的mRNA表达和抑制cyclin A的mRNA表达,而对cyclin E无明显作用.结论:TSA可通过诱导细胞凋亡及细胞周期阻滞而发挥体外抗膀胱癌作用,其作用机制可能涉及组蛋白乙酰化水平以及相关基因(p21CIP1/WAF1、cyclin A)表达的调控.     

慢性间断性缺氧对雄仔鼠肝胰岛素样生长因子-1基因组蛋白修饰的作用

目的:研究慢性间断性缺氧(CIH)时新生雄仔鼠肝形态学改变及胰岛素样生长因子-l(IGF-1)基因表达,探讨其表观遗传学分子机制.方法:将怀孕SD大鼠分为正常呼吸组(对照组)和间断缺氧组(缺氧组),建立CIH大鼠模型.分娩后取对照组和缺氧组1 d雄仔鼠肝组织,用电子显微镜观察肝组织的超微结构,免疫蛋白印迹和免疫组织化学...     

Photoperiod-induced neurotransmitter plasticity declines with aging: An epigenetic regulation?

Neuroplasticity has classically been understood to arise through changes in synaptic strength or synaptic connectivity. A newly discovered form of neuroplasticity, neurotransmitter switching, involves changes in neurotransmitter identity. Chronic exposure to different photoperiods alters the number of dopamine (tyrosine hydroxylase, TH+) and somatostatin (SST+) neurons in the paraventricular nucleus (PaVN) of the hypothalamus of adult rats and results in discrete behavioral changes. Here, we investigate whether photoperiod-induced neurotransmitter switching persists during aging and whether epigenetic mechanisms of histone acetylation and DNA methylation may contribute to this neurotransmitter plasticity. We show that this plasticity in rats is robust at 1 and at 3 months but reduced in TH+ neurons at 12 months and completely abolished in both TH+ and SST+ neurons by 18 months. De novo expression of DNMT3a catalyzing DNA methylation and anti-AcetylH3 assessing histone 3 acetylation were observed following short-day photoperiod exposure in both TH+ and SST+ neurons at 1 and 3 months while an overall increase in DNMT3a in SST+ neurons paralleled neuroplasticity reduction at 12 and 18 months. Histone acetylation increased in TH+ neurons and decreased in SST+ neurons following short-day exposure at 3 months while the total number of anti-AcetylH3+ PaVN neurons remained constant. Reciprocal histone acetylation in TH+ and SST+ neurons indicates the importance of studying epigenetic regulation at the circuit level for identified cell phenotypes. The findings may be useful for developing approaches for noninvasive treatment of disorders characterized by neurotransmitter dysfunction.     

Epigenetics explained: a topic “primer” for the epilepsy community by the ILAE Genetics/Epigenetics Task Force

Epigenetics refers broadly to processes that influence medium to long‐term gene expression by changing the readability and accessibility of the genetic code. The Neurobiology Commission of the International League Against Epilepsy (ILAE) recently convened a Task Force to explore and disseminate advances in epigenetics to better understand their role and intersection with genetics and the neurobiology of epilepsies and their co‐morbidities, and to accelerate translation of these findings into the development of better therapies. Here, we provide a topic primer on epigenetics, explaining the key processes and findings to date in experimental and human epilepsy. We review the growing list of genes with epigenetic functions that have been linked with epilepsy in humans. We consider potential practical applications, including using epigenetic signals as biomarkers for tissue‐ and biofluid‐based diagnostics and the prospects for developing epigenetic‐based treatments for epilepsy. We include a glossary of terms, FAQs and other supports to facilitate a broad understanding of the topic for the non‐expert. Last, we review the limitations, research gaps and the next challenges. In summary, epigenetic processes represent important mechanisms controlling the activity of genes, providing opportunities for insight into disease mechanisms, biomarkers and novel therapies for epilepsy.