表观遗传调控植物叶片衰老的研究进展

植物叶片衰老是一个非常重要的发育过程,涉及大分子的有序分解从而将营养物质从叶片转移到其他器官,对植物的生存和适应至关重要。叶片衰老主要受植物的发育调控,但同时也受内部和外部环境因素的影响,涉及高度复杂的基因调控网络和多层级的调控。近年来的研究表明表观遗传是调控植物叶片衰老的一种重要调控方式。该研究综述了植物叶片衰老过程中的表观遗传调控机制,包括组蛋白修饰、DNA甲基化、ATP依赖的染色质重塑和非编码RNA介导的调控,并对该领域今后的发展方向进行了展望。     

植物衰老过程中的表观遗传学调控

植物衰老是由内外环境因子共同调节的,发生在细胞、组织、器官和个体等多个层面上的衰退和死亡过程,涉及基因表达、蛋白翻译和修饰水平变化以及多种细胞结构和代谢途径的变化,并与激素和生物/非生物胁迫的应答等过程形成复杂的调控网络。近年的研究表明,表观遗传修饰参与了对植物衰老过程的调节,是除经典遗传学以研究基因序列影响生物学功能之外在非核酸序列改变的情况下导致可遗传的基因表达变化的机制。本文综述了植物衰老过程中表观遗传调控的机理,包括染色质构象变化、DNA甲基化、组蛋白修饰、ATP依赖的重构因子和非编码RNA介导的调控等,并对这一领域今后的发展方向进行了展望。     

衰老的表观遗传调控机制北大核心CSCD

表观遗传通过调控基因表达影响众多生命过程。大量的证据表明,表观遗传在衰老调控中也发挥重要的作用。本文介绍表观遗传的3种主要机制对衰老的调控作用,及其对衰老的2个主要特征的影响。同时,介绍热量限制介导的抗衰老作用的表观遗传的调控机制,和3种重要的抗衰老活性小分子及其如何通过表观遗传相关机制发挥抗衰老作用。本文结果为进一步研究表观遗传在衰老调控中的作用,以及发展抗衰老干预措施提供了理论依据和重要的参考资料。     

衰老的表观遗传调控机制

表观遗传通过调控基因表达影响众多生命过程。大量的证据表明,表观遗传在衰老调控中也发挥重要的作用。本文介绍表观遗传的3种主要机制对衰老的调控作用,及其对衰老的2个主要特征的影响。同时,介绍热量限制介导的抗衰老作用的表观遗传的调控机制,和3种重要的抗衰老活性小分子及其如何通过表观遗传相关机制发挥抗衰老作用。本文结果为进一步研究表观遗传在衰老调控中的作用,以及发展抗衰老干预措施提供了理论依据和重要的参考资料。     

生长素与植物叶片衰老调控

作为植物叶片发育的最后一个阶段,叶片衰老的启动和进程由遗传程序严格控制,并受到内外源不同因子的协同调控.多种植物激素对叶片的衰老发挥重要的调控作用,目前认为乙烯、脱落酸、水杨酸、茉莉酸和油菜素甾醇等激素促进植物叶片衰老,而细胞分裂素和赤霉素则抑制植物叶片衰老.传统观念曾认为生长素对植物叶片衰老起负调节作用,但近年来越来越多的实验证据表明生长素是叶片衰老的正调节因子.本文旨在对生长素在叶片衰老调控中的功能和研究历程进行简要综述,为进一步理解植物叶片衰老调控中的激素功能奠定基础.     

综述: 干细胞衰老的表观遗传调控

干细胞衰老理论认为,组织器官特异的成体干细胞随着衰老出现功能性衰退,从而导致组织器官生理功能的衰退甚至衰老相关疾病的发生.表观遗传机制通过精密调控基因表达,在成体干细胞的衰老过程中发挥着重要作用.近年来,机体衰老过程中成体干细胞的表观遗传调控已经成为衰老研究的热点.本综述主要总结了衰老过程中成体干细胞命运的表观遗传调控,并详细介绍了DNA甲基化与组蛋白共价修饰在成体干细胞衰老中的作用,以期为深入认识衰老本质、实现健康长寿提供启示.     

干细胞衰老的表观遗传调控

干细胞衰老理论认为,组织器官特异的成体干细胞随着衰老出现功能性衰退,从而导致组织器官生理功能的衰退甚至衰老相关疾病的发生.表观遗传机制通过精密调控基因表达,在成体干细胞的衰老过程中发挥着重要作用.近年来,机体衰老过程中成体干细胞的表观遗传调控已经成为衰老研究的热点.本综述主要总结了衰老过程中成体干细胞命运的表观遗传调控,并详细介绍了DNA甲基化与组蛋白共价修饰在成体干细胞衰老中的作用,以期为深入认识衰老本质、实现健康长寿提供启示.     

衰老过程中的表观遗传调控

生物体衰老表现为性成熟后生理功能的逐渐衰退,最终引发疾病和死亡。表观遗传调控的紊乱作为衰老的一个重要特征,暗示可以通过干预表观遗传调控来延缓衰老并治疗衰老相关疾病。现就衰老过程中的表观遗传调控的最新进展作一综述。     

叶片衰老过程中的蛋白激酶和蛋白磷酸酶

衰老是受遗传程序严格控制的植物个体发育过程中的一个必经阶段,由特殊发育信号通过一定的信号传导路径来启动和控制。研究发现,蛋白激酶和蛋白磷酸酶所介导的可逆磷酸化反应在叶片衰老信号传递和衰老的启动和进程控制过程中发挥了重要作用。本文对近年参与叶片衰老调控的蛋白激酶和蛋白磷酸酶基因的分离鉴定及功能研究进行了综述。     

表观遗传修饰影响花青苷合成研究进展

花青苷是广泛存在于植物中的一类重要的类黄酮化合物,对植物生长、代谢、应激等方面具有重要作用。在植物生长发育过程中,花青苷使植物的花和果实呈现出丰富色彩的颜色,从而吸引昆虫传粉和动物采食,便于结种和传播;在植物代谢应激反应中,花青苷使植物具有抵御低温、干旱、真菌感染,防御紫外线伤害、虫害等能力。花青苷生物合成通路受相关结构基因和转录因子的调控机制已被解析得十分清楚,近几年研究发现,植物花青苷生物合成相关基因受到表观调控,从而影响花青素苷的合成。表观遗传学是目前生命科学领域研究的热点之一,本文结合最新的植物花青苷合成表观遗传学研究进展,综述了花青苷合成过程中的表观遗传修饰以及基因编辑技术在表观遗传学研究中的应用,以期利用表观遗传手段为花色育种改良提供新思路。     

Epigenetic control of cellular senescence in disease: opportunities for therapeutic intervention

Understanding how senescence is established and maintained is an important area of study both for normal cell physiology and in tumourigenesis. Modifications to N-terminal tails of histone proteins, which can lead to chromatin remodelling, appear to be key to the regulation of the senescence phenotype. Epigenetic mechanisms such as modification of histone proteins have been shown to be sufficient to regulate gene expression levels and specific gene promoters can become epigenetically altered at senescence. This suggests that epigenetic mechanisms are important in senescence and further suggests epigenetic deregulation could play an important role in the bypass of senescence and the acquisition of a tumourigenic phenotype. Tumour suppressor proteins and cellular senescence are intimately linked and such proteins are now known to regulate gene expression through chromatin remodelling, again suggesting a link between chromatin modification and cellular senescence. Telomere dynamics and the expression of the telomerase genes are also both implicitly linked to senescence and tumourigenesis, and epigenetic deregulation of the telomerase gene promoters has been identified as a possible mechanism for the activation of telomere maintenance mechanisms in cancer. Recent studies have also suggested that epigenetic deregulation in stem cells could play an important role in carcinogenesis, and new models have been suggested for the attainment of tumourigenesis and bypass of senescence. Overall, proper regulation of the chromatin environment is suggested to have an important role in the senescence pathway, such that its deregulation could lead to tumourigenesis.     

Epigenetic mechanisms in senescence,immortalisation and cancer

Cancer is controlled not only by genetic events but also by epigenetic events. The active acquisition of epigenetic changes is a poorly understood but very important process in mammalian development, differentiation, and disease. It is well established that epigenetic events are controlled by a specific subgroup of proteins, such as DNA methyltransferases, histone acetylases histone lysine methyltransferases or histone deacetylases, that influence methylation or acetylation patterns to modulate gene expression. We and others have identified S‐adenosylhomocysteine hydrolase in a high‐throughput genetic screen focused on discovering novel genes whose inhibition induces immortalisation of primary cells. Herein, we address the importance of genes involved in epigenetic mechanisms during senescence and how their effects might determine senescence bypass and immortalisation. The ways in which genes that regulate epigenetic mechanisms might modulate senescence/immortalisation and how these pathways could influence cancer development are explored. Overall, epigenetic modifications seem to play a major role in cancer, influencing tumour outcome by interfering with key senescence pathways.     

Epigenetic and small RNA regulation of senescence

Leaf senescence is regulated through a complex regulatory network triggered by internal and external signals for the reprogramming of gene expression. In plants, the major developmental phase transitions and stress responses are under epigenetic control. In this review, the underlying molecular mechanisms are briefly discussed and evidence is shown that epigenetic processes are also involved in the regulation of leaf senescence. Changes in the chromatin structure during senescence, differential histone modifications determining active and inactive sites at senescence-associated genes and DNA methylation are addressed. In addition, the role of small RNAs in senescence regulation is discussed.     

Polycomb蛋白复合体对细胞衰老的表观遗传学调控

细胞衰老在表观遗传学上的调控越来越受到人们的关注.Polycomb蛋白复合体(polycomb group proteins)通过对组蛋白的修饰,尤其是甲基化修饰发挥对靶基因的沉默作用,并因此广泛参与到发育、增殖、分化以及肿瘤发生等重要生命过程.目前,有一系列的研究报道了polycomb的各组份参与了细胞衰老的调控.本文对polycomb发挥基因沉默作用机制的最新研究进展进行了归纳总结,并以衰老过程中的重要分子p16为重点,详细介绍了polycomb调节p16表达,影响细胞衰老进程的机制.研究表明,多种polycomb成员同时结合在p16INK4a基因座,它们的结合表现出相互依赖的同时又有各自的作用.这为进一步深入理解细胞衰老提供了表观遗传学的证据.     

The PPARγ‐SETD8 axis constitutes an epigenetic,p53‐independent checkpoint on p21‐mediated cellular senescence

Cellular senescence is a permanent proliferative arrest triggered by genome instability or aberrant growth stresses, acting as a protective or even tumor‐suppressive mechanism. While several key aspects of gene regulation have been known to program this cessation of cell growth, the involvement of the epigenetic regulation has just emerged but remains largely unresolved. Using a systems approach that is based on targeted gene profiling, we uncovered known and novel chromatin modifiers with putative link to the senescent state of the cells. Among these, we identified SETD8 as a new target as well as a key regulator of the cellular senescence signaling. Knockdown of SETD8 triggered senescence induction in proliferative culture, irrespectively of the p53 status of the cells; ectopic expression of this epigenetic writer alleviated the extent doxorubicin‐induced cellular senescence. This repressive effect of SETD8 in senescence was mediated by directly maintaining the silencing mark H4K20me1 at the locus of the senescence switch gene p21. Further in support of this regulatory link, depletion of p21 reversed this SETD8‐mediated cellular senescence. Additionally, we found that PPARγ acts upstream and regulates SETD8 expression in proliferating cells. Downregulation of PPARγ coincided with the senescence induction, while its activation inhibited the progression of this process. Viewed together, our findings delineated a new epigenetic pathway through which the PPARγ‐SETD8 axis directly silences p21 expression and consequently impinges on its senescence‐inducing function. This implies that SETD8 may be part of a cell proliferation checkpoint mechanism and has important implications in antitumor therapeutics.     

Senescence and epigenetic dysregulation in cancer

Mammalian cells have a finite proliferative lifespan, at the end of which they are unable to enter S phase in response to mitogenic stimuli. They undergo morphological changes and synthesize an altered repertoire of cell type-specific proteins. This non-proliferative state is termed replicative senescence and is regarded as a major tumor suppressor mechanism. The ability to overcome senescence and obtain a limitless replicative potential is called immortalization, and considered to be one of the prerequisites of cancer formation. While senescence mainly represents a genetically governed process, epigenetic changes in cancer have received increasing attention as an alternative mechanism for mediating gene expression changes in transformed cells. DNA methylation of promoter-containing CpG islands has emerged as an epigenetic mechanism of silencing tumor suppressor genes. New insights are being gained into the mechanisms causing aberrant methylation in cancer and evidence suggests that aging is accompanied by accumulation of cells with aberrant CpG island methylation. Aberrant methylation may contribute to many of the physiological and pathological changes associated with aging including tumor development. Finally, we describe how genes involved in promoting longevity might inhibit pathways promoting tumorigenesis.