植物转基因沉默

转基因沉默分为两种水平:第一种是转录水平上的基因沉默,发生原因主要是位置效应、异染色质化以及甲基化;第二种是转录后水平上的基因沉默,发生原因是通过对靶标RNA进行特异性降解而使基因失活,并就此研究提出RNA阈值模型、异常RAN模型、分子间(内)配对模型与RNA干涉模型来解释这种现象产生的机制。     

DNA甲基化异常与肿瘤发生的研究

DNA甲基化是真核生物DNA的正常内源性修饰方式 ,它由DNA甲基化转移酶催化发生。但DNA甲基化异常在肿瘤发生中却起着极为重要的作用 ,它主要表现为抑癌基因高甲基化所致的基因失活和原癌基因低甲基化所致的基因激活 ,引起与细胞增殖、分化相关基因表达异常 ,造成细胞恶变形成肿瘤。文章总结了DNA甲基化异常对肿瘤相关基因表达的影响 ,在肿瘤发生中的可能机制及针对高甲基化的治疗方案     

甲醛、组蛋白（脱）甲基化与学习记忆

组蛋白的甲基化与脱甲基是调控DNA特定基因“开”与“关”的主要分子机制之一,与哺乳动物表观遗传密切相关。研究表明,组蛋白的可逆共价修饰,也是记忆与遗忘的分子调控机制。甲醛作为甲基化供体,参与了组蛋白修饰的关键环节。因此,甲醛代谢失调,可能影响组蛋白甲基化与脱甲基,也影响DNA甲基化与脱甲基,这可能是老年认知损伤的因素之一。     

Comparative features of colorectal and gastric cancers with microsatellite instability in Chinese patients

Objective  

The purpose of this study was to determine the unique and universal features of microsatellite instability-high (MSI-H) colorectal cancer (CRC) and MSI-H gastric cancer (GC) in the Chinese population.     

MKRN3 regulates the epigenetic switch of mammalian puberty via ubiquitination of MBD3

Central precocious puberty (CPP) refers to a human syndrome of early puberty initiation with characteristic increase in hypothalamic production and release of gonadotropin-releasing hormone (GnRH). Previously, loss-of-function mutations in human MKRN3, encoding a putative E3 ubiquitin ligase, were found to contribute to about 30% of cases of familial CPP. MKRN3 was thereby suggested to serve as a ‘brake’ of mammalian puberty onset, but the underlying mechanisms remain as yet unknown. Here, we report that genetic ablation of Mkrn3 did accelerate mouse puberty onset with increased production of hypothalamic GnRH1. MKRN3 interacts with and ubiquitinates MBD3, which epigenetically silences GNRH1 through disrupting the MBD3 binding to the GNRH1 promoter and recruitment of DNA demethylase TET2. Our findings have thus delineated a molecular mechanism through which the MKRN3–MBD3 axis controls the epigenetic switch in the onset of mammalian puberty.     

Development of mouse preimplantation embryos in space

The development of life beyond planet Earth is a long-standing quest of the human race, but whether normal mammalian embryonic development can occur in space is still unclear. Here, we show unequivocally that preimplantation mouse embryos can develop in space, but the rate of blastocyst formation and blastocyst quality are compromised. Additionally, the cells in the embryo contain severe DNA damage, while the genome of the blastocysts developed in space is globally hypomethylated with a unique set of differentially methylated regions. The developmental defects, DNA damage and epigenetic abnormalities can be largely mimicked by the treatment with ground-based low-dose radiation. However, the exposure to simulated microgravity alone does not cause major disruptions of embryonic development, indicating that radiation is the main cause for the developmental defects. This work advances the understanding of embryonic development in space and reveals long-term extreme low-dose radiation as a hazardous factor for mammalian reproduction.     

DNA甲基化异常与肿瘤间关系的研究进展

DNA的甲基化及甲基化异常在人体发育和肿瘤的发生中起着至关重要的作用。文中主要综述了几十年来人们对 DNA甲基化异常与基因转录及肿瘤发生之间关系的研究进展 ,尤其是最近的研究突破。     

多变环境和复杂事件的表观遗传记录是细胞的衰老之源（英文）

虽然表观遗传和衰老的关联性已经被广泛接受,但是两者之间内在的因果关系需要深度的理论阐述和分析.本文通过分析环境与表观遗传相互作用及其过程的本质特征,证明表观遗传记录多变的细胞环境和复杂的细胞事件是细胞的衰老之源.细胞周围环境以及所经历事件可通过表观修饰激活或抑制染色体上各个基因的表达,从而对染色体模板以及基因表达模式进行塑造.外在环境和细胞历史的多变性以及内在冲突性由此被逐渐记录在染色体模板上,整体上导致染色体模板以及基因表达模式的混乱和耗散.这将导致细胞表观熵(类似于Shannon信息熵)不可避免地逐渐衰减,其混乱度可通过细胞分裂而进一步被稳定积累、记忆和扩增.另外,表观修饰应对外在环境的变化存在滞后性和一定的不可逆性,加剧了表观熵的衰退.