Cooperation of MLL1 and Jun in controlling H3K4me3 on enhancers in colorectal cancer.

BACKGROUND: Enhancer dysregulation is one of the important features for cancer cells. Enhancers enriched with H3K4me3 have been implicated to play important roles in cancer. However, their detailed features and regulatory mechanisms have not been well characterized. RESULTS: Here, we profile the landscape of H3K4me3-enriched enhancers (m3Es) in 43 pairs of colorectal cancer (CRC) samples. M3Es are widely distributed in CRC and averagely possess around 10% of total active enhancers. We identify 1322 gain variant m3Es and 367 lost variant m3Es in CRC. The target genes of the gain m3Es are enriched in immune response pathways. We experimentally prove that repression of CBX8 and RPS6KA5 m3Es inhibits target gene expression in CRC. Furthermore, we find histone methyltransferase MLL1 is responsible for depositing H3K4me3 on the identified Vm3Es. We demonstrate that the transcription factor AP1/JUN interacts with MLL1 and regulates m3E activity. Application of a small chemical inhibitor for MLL1 activity, OICR-9429, represses target gene expression of the identified Vm3Es, enhances anti-tumor immunity and inhibits CRC growth in an animal model. CONCLUSIONS: Taken together, our study illustrates the genome-wide landscape and the regulatory mechanisms of m3Es in CRC, and reveals potential novel strategies for cancer treatment.

Removal of epigenetic repressive mark on inflammatory genes in fat liver.

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The detailed epigenomic changes during fat accumulation in liver are not clear yet. Here, we performed ChIP-Seq analysis in the liver tissues of high-fat diet and regular chow diet mice and investigated the dynamic landscapes of H3K27ac and H3K9me3 marks on chromatin. We find that the activated typical enhancers marked with H3K27ac are enriched on lipid metabolic pathways in fat liver; however, super enhancers do not change much. The regions covered with H3K9me3 repressive mark seem to undergo great changes, and its peak number and intensity both decrease in fat liver. The enhancers located in lost H3K9me3 regions are enriched in lipid metabolism and inflammatory pathways; and motif analysis shows that they are potential targets for transcription factors involved in metabolic and inflammatory processes. Our study has revealed that H3K9me3 may play an important role during the pathogenesis of NAFLD through regulating the accessibility of enhancers.

[An investigation of fast thermolysis of GAP/AP system by FTIR spectroscopy].

The rapid pyrolysis of GAP/AP system under simulated combustion conditions was investigated by an on-line analysis, i. e. so called T-Jump/FTIR. The results show that the compositions of the main gaseous products for pyrolysis are changed, in comparison with the pyrolyses of single, which indicates that the interactions occur between the components of GAP/AP system. From an obvious effect of pressure on the main gaseous products for GAP/AP pyrolysis it is shown that the interactions between GAP and AP components arise from the gaseous products of AP and both the reactions in gas phase and in gas/condensed phase occur in the GAP/AP mixed system. The interactions between GAP and AP are not affected by test temperature. It is considered that the real time analysis of gaseous products of energetic material pyrolysis under simulated combustion conditions would be carried out by T-Jump/FTIR on-line analysis technique and from microcosmic reaction a technical approach used to explore the rapid pyrolysis of energetic materials and interactions between their components at high temperature and pressure would be developed by the on-line analysis technique from microcosmic reaction.

[An investigation on fast thermolysis of ammonium perchlorate (AP) by FTIR spectroscopy].

The fast thermolysis processes of ammonium perchlorate (AP) and its chemical reaction mechanism under certain simulated conditions of combustion were systematically studied by means of T-Jump/FTIR technique. AP was flash-pyrolyzed under different pressure nitrogen atmosphere, with the heating rate of 1000 K x s(-1) and the set temperatures of 874 and 1 274 K. Thereafter, the real time species and concentration of its gaseous products were obtained and identified by using rapid scanning Fourier transform infrared (FTIR) in-situ spectroscopy. It was indicated that the main gaseous products of AP thermolysis is composed of NO2, N2O, NO, HCl and NClO. Interestingly, the values of N2O/NO2, NO/NO2 and NO/NClO are increased while the test temperature or pressure is elevated. It is suggested that the transformation of condensed phase and heterogeneous gas/condensed phase was probably arises and the "following reactions" among the main gaseous products may also take place in the fast thermolysis process of AP.

Effects of Bi-NTO complex on thermal behaviors, nonisothermal reaction kinetics and burning rates of NG/TEGDN/NC propellant.

A bismuth 3-nitro-1,2,4-triazol-5-one (Bi-NTO) complex was prepared and characterized, and its effects on the thermal behaviors, non-isothermal decomposition reaction kinetics, and burning rates of the double-base (DB) propellant containing the mixed ester of triethyleneglycol dinitrate (TEGDN) and nitroglycerin (NG) with Bi-NTO complex as a ballistic modifier were investigated by thermogravimetry and derivative thermogravimetry (TG-DTG), and differential scanning calorimetry (DSC). The results show that Bi-NTO complex can increase the decomposition heat by 140 J g(-1), and it can change the decomposition reaction mechanism function, the kinetic parameters and kinetic equation of the propellant under 0.1 MPa. Combustion experiment shows that Bi-NTO complex can increase the burning rate and reduce the pressure exponent of the NG/TEGDN/NC propellant effectively, with the increase of the catalysis efficiency by 40%.

Effects of pressure and TEGDN content on decomposition reaction mechanism and kinetics of DB gun propellant containing the mixed ester of TEGDN and NG.

The effects of pressure and triethyleneglycol dinitrate (TEGDN) content on the decomposition reaction mechanism and kinetics of the double-base (DB) gun propellant composed of mixed ester of TEGDN and nitroglycerin (NG), and nitrocellulose (NC) were investigated by high-pressure differential scanning calorimetry (PDSC). The results show that the high pressure can decrease the DSC peak temperature, increase the decomposition heat; with the increase in the content of TEGDN, the decomposition heat decreases below 2MPa and rises at 4MPa. The high pressure can change the decomposition reaction mechanism and the kinetics of the DB gun propellant under 0.1MPa; the high TEGDN content does not change the mechanism functions, and the kinetic equation has a little difference between the sample and the control propellant; the high pressure makes the critical temperature (T(be)) of thermal explosion of the sample decrease, while the high TEGDN content make it present a increasing trend, and the DB gun propellant containing high content of TEGDN has a better thermal stability.