Regulation of zygotic gene activation in the preimplantation mouse embryo: Global activation and repression of gene expression

Superimposed on the activation of the embryonic genome in the preimplantation mouse embryo is the formation of a transcriptionally repressive state during the two-cell stage. This repression appears mediated at the level of chromatin structure, because it is reversed by inducing histone hyperacetylation or inhibiting the second round of DNA replication. We report that of more than 200 amplicons analyzed by mRNA differential display, about 45% of them are repressed between the two-cell and four-cell stages. This repression is scored as either a decrease in amplicon expression that occurs between the two-cell and four-cell stages or on the ability of either trichostatin A tan inhibitor of histone deacetylases) or aphidicolin tan inhibitor of replicative DNA polymerases) to increase the level of amplicon expression. Results of this study also indicate that about 16% of the amplicons analyzed likely are novel genes whose sequence doesn't correspond to sequences in the current databases, whereas about 20% of the sequences expressed during this transition likely are repetitive sequences. Lastly, inducing histone hyperacetylation in the two-cell embryos inhibits cleavage to the four-cell stage. These results suggest that genome activation is global and relatively promiscuous and that a function of the transcriptionally repressive state is to dictate the appropriate profile of gene expression that is compatible with further development.

Rapid evolution of an X-linked microRNA cluster in primates

MicroRNAs (miRNAs) are a growing class of small RNAs ( about 22 nt) that play crucial regulatory roles in the genome by targeting mRNAs for cleavage or translational repression. Most of the identified miRNAs are highly conserved among species, indicating

Stability and molecular modeling of triplex DNA inhibiting DNA binding protein binding to the core promoter of hepatitis B virus.

Two three-dimensional structure models of the 21nt oligodeoxyribonucleotides, CPI (G3TG-2TGT2G5TG2TGT) and CP3 (TGTG2TGST2GTG2TG3), were constructed by InsightII (MSI) software in IRIS Indigo2 (SGI) workstation using the crystal structure of TAT tripler formation as the template. The initial structures subsequently were minimized by molecular mechanics. The final structures were believed as the dominant conformation. The results showed that the energy of CP1 is lower than that of CP3, and the former is more stable than the latter. Moreover, the results further proved that the 21nt oligodeoxyribo-nucleotide CP1 stably combines with the core promoter (Cp) fragment of hepatitis B virus (HBV) to form a tripler DNA, and CP1 specifically inhibits a specific cellular factor (DNA binding protein) binding to Cp fragment. These results indicated that specific repression of gene transcription of HBV DNA might be possible by tripler-formation DNA.

Zebrafish thymidylate synthase binds to its own mRNA in vitro and in vivo

Thymidylate synthase (TS), an essential enzyme for DNA de novo synthesis, is a critical therapeutic target in cancer therapy. Previous study has shown that TS was able to bind to its own mRNA in human and E.coli, resulting in translational repression. Zebrafish is the best animal model for vertebrate study. In order to study the regulatory mechanism of zebrafish TS, the enzyme were expressed in E. coli BL21 (DE3) and it was purified to homogeneity. Electrophoretic mobility shift assay (EMSA) was used to detect the interaction of zebrafish TS protein and its own TS transcript in vitro and the results showed that zebrafish TS could bound with its own mRNA specifically. Further study revealed that zebrafish TS was able to interact with its own mRNA in vivo using immunoprecipitation : RT-PCR technique. The results provide evidence that zebrafish may be developed as an useful model for studying the anti-metabolism agents.

A型、D型人格影响冠心病预后的心理生理机制

Coronary heart disease （CHD）is a common cardiovascular disease in the elderly, is also a typical psychosomatic disease. Personality factors are very important in many psychological factors impacting on the prognosis of patients with CHD. The most influential personality factors to CHD are Type A and Type D personality. The previous research has shown that although Type A personality increased the prevalence of CHD, it cannot predict the development and prognosis after diagnosis. In contradict, Type D personality can predict prognosis. There is still no clinic-based or theory-based answer to the question: Why Type A personality cannot predict the outcome while Type D personality could predict the prognosis independently. The current research conducted a systematic investigation to the above question, which included one comparison study between CHD patients and control group, and four studies on reaction experiment and answered the question: why Type A personality cannot predict whereas Type D personality could effectively predict prognosis of CHD. The findings of the current research were: Type A and Type D personality influence CHD prognosis through different psychological mechanisms: both dimensions of Type D personality have direct influence on social support, whereas neither dimensions of Type A personality related to social support, directly of indirectly. Negative affection component of Type D personality significantly related to anxiety and depression, Social repression significantly related to anxiety but not depression. Both dimensions of Type A personality significantly related to anxiety but not depression. Neither under rest or diaphragmatic breathing conditions, Type A personality had no significant influence on vestibular autonomic reaction among healthy young males. Neither Type A nor Type D personality had significant influence on vestibular autonomic reaction among old CHD patients under rest condition. Type D personality predicted lower sympathetic excitation under rest condition, and lower cardiac vagal tone under diaphragmatic breathing condition among healthy young males. When actively reacted to stimuli (math calculation) under rest condition, Type A personality increased sympathetic excitation among healthy young males. When actively reacted to stimuli (math calculation) under diaphragmatic breathing condition, Type A personality increased cardiac vagal tone among the same group of subjects. When actively reacted to stimuli under neither condition, Type D personality showed no significant influence on vestibular autonomic reaction among young males. When passively reacted to stimuli under neither condition, Type A personality showed no significant influence on vestibular autonomic reaction among young males. When passively stimulated followed rest, Type D personality increased sympathetic excitation and decreased cardiac vagal tone among young males. When passively stimulated followed diaphragmatic breathing, Typed showed no significant influence on vestibular autonomic reaction among young males. The above results indicated that Type A and Type D personalities had different psychological mechanisms to the outcome of CHD treatment: neither dimensions of Type A personality had direct or indirect effects on social support; both dimensions of Type D personality had direct and indirect effects on social support. Negative affection component of Type D personality significantly related to anxiety and depression, Social repression significantly related to anxiety but not depression. Both dimensions of Type A personality significantly related to anxiety but not depression. Social support positively related to the outcome after CHD treatment. The biological mechanisms of Type A and Type B personality to CHD prognosis differed in the following ways: Type A personality increased sympathetic excitation when actively stimulated, but had no influence when passively stimulated among young male subjects. When passively stimulated after rest, Type D personality predicted high sympathetic excitation and low cardiac vagal tone among young males, but not vestibular autonomic reaction among young males. Key words: Type A personality, Type D personality, Coronary Heart Disease (CHD), Prognosis, Psychobiological Mechanisms