Chromatin states responsible for the regulation of differentially expressed genes under 60Co~γ ray radiation in rice.

BACKGROUND: The role of histone modifications in the DNA damage response has been extensively studied in non-plant systems, including mammals and yeast. However, there is a lack of detailed evidence showing how chromatin dynamics, either an individual mark or combined chromatin states, participate in regulating differentially expressed genes in the plant DNA damage response. RESULTS: In this study, we used RNA-seq and ChIP-seq to show that differentially expressed genes (DEGs), in response to ionizing radiation (IR), might be involved in different pathways responsible for the DNA damage response. Moreover, chromatin structures associated with promoters, exons and intergenic regions are significantly affected by IR. Most importantly, either an individual mark or a certain chromatin state was found to be highly correlated with the expression of up-regulated genes. In contrast, only the chromatin states, as opposed to any individual marks tested, are related to the expression of the down-regulated genes. CONCLUSIONS: Our findings demonstrate that IR-related DEGs are modulated by distinct epigenetic mechanisms. Either chromatin states or distinct histone dynamics may act sequentially or in combination in regulating up-regulated genes, but the complex chromatin structure is mainly responsible for the expression of down-regulated genes. Thus, this study provides new insights into how up- and down-regulated genes are epigenetically regulated at the chromatin levels, thereby helping us to understand distinct epigenetic mechanisms that function in the plant DNA damage response.

NF-κB signaling inhibition and anticancer activities of LLDT-246 on human colorectal cancer HCT-116 cells in vitro.

Triptolide attracts attention for its anti-inflammatory, immune modulation, anti-proliferative and pro-apoptotic activity, but the clinical application of triptolide is restricted by its serious toxicity. Here, we demonstrate LLDT-246, a new triptolide derivative, exhibited a little more potent activity of NF-κB inhibition and cytotoxicity whether acting alone or in combination with TNF-α on colorectal cancer HCT-116 cells than its maternal compound, and showed low toxic to non-cancer cells. Mechanism study revealed that LLDT-246 inhibited phosphorylation of AKT, p-GSK3ß and p-mTOR, however, no significant effects were found on the level of p-ERK and p-JNK, along with HSP70, indicating LLDT-246 indirectly affects NF-κB and suppresses NF-κB signaling largely by interpreting AKT/GSK3ß/mTOR pathway. Altogether, LLDT-246 is a promising anticancer derivative of triptolide, further studies in vivo and about detailed mechanism of LLDT-246 is required in the future.

The evolutionary history of PDR in Brachypodium distachyon polyploids.

The ATP-binding cassette transporter genes include the pleiotropic drug resistance (PDR) family found only in fungi and plants. These transporters transport toxic compounds across biological membranes. Here, we investigated the evolution of the PDR1 gene in Brachypodium distachyon, a widely distributed temperate grass species that belongs to the Poaceae (Gramineae) family, which also contains the domesticated cereal crops. Because this species has multiple ploidy levels, investigating PDR1 evolution in B. distachyon will offer insights into the formation and evolution of polyploidy. From 23 B. distachyon ecotypes, 39 PDR1 homologs were identified. All ecotypes had either one or two PDR1 copies. Based on restriction site analysis, the PDR1 homologs were classified as E or H type. All but one diploid and tetraploid ecotypes had only a single H type PDR1. All but one hexaploid ecotypes had both an E and a H type PDR1. Phylogenetic analysis revealed that each type formed a well-supported cluster. The two PDR1 types appeared to evolve differently. These different evolutionary patterns could indicate a difference in age between the two types or might indicate different mutation rates or selection pressures on the two types. The phylogenetic analysis also revealed that the hexaploid ecotypes shared a genomic origin for their E type PDR1, but there were multiple origins for hexaploid H type PDR1 homologs. Overall, the results suggest that tetraploid and hexaploid might be misnomers in B. distachyon and suggest a complex polyploidization history during B. distachyon evolution.