The establishment and faithful maintenance of epigenetic information in the context of chromatin are crucial for a great number of biologic phenomena, including position effect variegation, Polycomb silencing, X-chromosome inactivation and genomic imprinting. However, mechanisms by which that the correct histone modification patterns propagate into daughter cells during mitotic divisions remain to be elucidated. The partitioning pattern of parental histone H3-H4 tetramers is a critical question toward our understanding of the epigenetic inheritance. In this review, we discuss why the histone H3-H4 tetramer split decision matters.
In addition to the post-translational modifications of histone proteins, emerging literature suggests that the mosaic nucleosomes formed by incorporation of various histone variants provide another mechanism for modifying chromatin structure and function. The locally defined chromatin by histone variants is involved in transcriptional regulation, DNA repair, centromere packaging, maintenance of pericentromeric heterochromatin, stress responses, temperature sensing, development, and many other biological processes. Here, we review the universal histone variants in H2A, H3 and H1 families and their roles in epigenetics.
The centromere is a highly organized structure mainly composed of repeat sequences, which make this region extremely difficult for sequencing and other analyses. It plays a conserved role in equal division of chromosomes into daughter cells in both mitosis and meiosis. However, centromere sequences show notable plasticity. In a dicentric chromosome, one of the centromeres can become inactivated with the underlying DNA unchanged. Furthermore, formerly inactive centromeres can regain activity under certain conditions. In addition, neocentromeres without centromeric repeats have been found in a wide spectrum of species. This evidence indicates that epigenetic mechanisms together with centromeric sequences are associated with centromere specification.
Histone ubiquitination plays a critical role in the regulation of transcription, and histone H2B monoubiquitination (H2Bub1) is mainly associated with transcriptional activation. Recent studies in yeast, humans, and
Dosage compensation refers to the equal expression between the sexes despite the fact that the dosage of the X chromosome is different in males and females. In
Mediator, a conserved multiprotein complex in animals, plants, and fungi, is a cofactor of RNA polymerase II (Pol II). It is known to promote basal Pol II-mediated transcription as well as bridge sequence-specific transcriptional regulators and Pol II to integrate regulatory information. Pol II transcribes not only protein-coding genes but also intergenic regions to generate noncoding RNAs such as small RNAs (microRNAs and small interfering RNAs) and long noncoding RNAs. Intriguingly, two plant-specific polymerases, Pol IV and Pol V, have evolved from Pol II and play a role in the production of small interfering RNAs and long noncoding RNAs at heterochromatic regions to maintain genome stability through transcriptional gene silencing (TGS). Recent studies have defined the composition of the plant Mediator and evaluated its role in noncoding RNA production in relationship to Pol II, Pol IV and Pol V. Here, we review the functions of Mediator and that of noncoding RNAs generated by Pol II, Pol IV and Pol V in plants, and discuss a role of Mediator in epigenetic regulation via noncoding RNA production.
DNA methylation, a major event in epigenetics, plays an essential role in the control of gene expression. Increasing evidence suggests that long and short non-coding RNAs are involved extensively in plants to direct the establishment, spread, and removal of DNA cytosine methylation throughout their genomes. Yet, little has been known about the role of microRNAs (miRNAs) in DNA methylation although the role of small interfering RNAs (siRNAs) in DNA methylation has been well established. Several recent studies, however, provided the evidence for miRNA-directed DNA methylation in plants, and the working mechanisms still need to be fully explored. In this review, we highlight the key features of miRNA-directed DNA methylation in plants and provide insight into the complexities of such an event in plants. The interaction between miRNAs and the epigenetic machinery and the future potential research questions are briefly discussed.
RNA-mediated silencing in plants can spread from cell to cell and over a long distance, and such mobile silencing has been extensively studied in the past decade. However, major questions remain as to what is the exact nature of the mobile silencing signals, how the components of the RNA-directed DNA methylation pathway are involved, and why systemic spread of silencing has only been observed for transgenes but not endogenous genes. In this review, we provide an overview of the current knowledge on mobile gene silencing in plants and present a model where systemic silencing involves long nuclear RNA transcripts that serve as a template to amplify primary siRNA signals.
Loss or gain of chromosomes, a condition known as aneuploidy, is a common feature of tumor cells and has therefore been proposed as the driving force for tumorigenesis. Such chromosomal instability can arise during mitosis as a result of mis-segregation of the duplicated sister chromatids to the two daughter cells. In normal cells, mis-segregation is usually prevented by the spindle assembly checkpoint (SAC), a sophisticated surveillance mechanism that inhibits mitotic exit until all chromosomes have successfully achieved bipolar attachment to spindle microtubules. Complete abrogation of SAC activity is lethal to normal as well as to tumor cells, as a consequence of massive chromosome mis-segregation. Importantly, many human aneuploid tumor cells exhibit a weakened SAC activity that allows them to tolerate gains or losses of a small number of chromosomes; and interfering with this SAC residual activity may constitute a suitable strategy to kill cancer cells. This review focuses on the potential link between SAC and tumorigenesis, and the therapeutic strategy to target the SAC for cancer treatment.