The influence of FKBP5 genotype on expression of FKBP5 and other glucocorticoid‐regulated genes,dependent on trauma exposure

The FK506 binding protein 51 (FKBP5), an intrinsic regulator of the glucocorticoid receptor, has been associated with pathological behaviors particularly in the context of childhood trauma (CT), via a putatively regulatory polymorphism, rs1360780. However, trans‐ and cis‐acting effects of this locus and its interaction with CT are incompletely understood. To study its effects on the expression of glucocorticoid‐regulated genes including FKBP5, we used lymphoblastoid cell lines (LCLs) derived from 16 CT‐exposed patients with greater than two substance dependence/suicidal behavior diagnoses (casesCT+) and 13 non‐CT‐exposed controls (controlsCT?). This study in LCLs measures long‐term trait‐like differences attributable to genotype or lasting epigenetic modification. Through analysis of differential allelic expression (DAE) using an FKBP5 3′‐UTR reporter single nucleotide polymorphism (SNP), rs3800373, that is in strong linkage disequilibrium with rs1360780, we confirmed that the rs1360780 risk allele (A) (or conceivably that of a linked SNP) leads to higher FKBP5 expression in controlsCT?. Intriguingly, casesCT+ did not show DAE, perhaps because of a genotype‐predicted difference in FKBP5 DNA methylation restricted to casesCT+. Furthermore, through correlation analyses on FKBP5 expression at baseline and after induction by dexamethasone, we observed that casesCT+ had lower induction of FKBP5 expression, indicating that overall they may have strong ultra‐short negative‐feedback. Only casesCT+ showed an effect of rs1360780 genotype on expression of FKBP5 and other glucocorticoid‐regulated genes. Together, these results confirm that the rs1360780 locus alters FKBP5 expression and further that in trans‐fashion this locus affects the expression of other glucocorticoid‐regulated genes after a glucocorticoid challenge. The CT exposure appears to be essential for trans‐effects of rs1360780 on glucocorticoid‐regulated genes.     

Molecular mechanisms controlling fructose‐specific memory and catabolite repression in lactose metabolism by Streptococcus mutans

Lactose is an abundant dietary carbohydrate metabolized by the dental pathogen Streptococcus mutans. Lactose metabolism presents both classic diauxic behaviors and long‐term memory, where the bacteria can pause for >11 h before initiating growth on lactose. Here, we explored mechanisms contributing to unusual aspects of regulation of the lac operon. The fructose‐phosphate metabolites, F‐1‐P and F‐6‐P, could modulate the DNA‐binding activities of the lactose repressor. Recombinant LacR proteins bound upstream of lacA and Gal‐6‐P induced the formation of different LacR‐DNA complexes. Deletion of lacR resulted in strain‐specific growth phenotypes on lactose, but also on a number of mono‐ and di‐saccharides that involve the glucose‐PTS or glucokinase in their catabolism. The phenotypes were consistent with the novel findings that loss of LacR altered glucose‐PTS activity and expression of the gene for glucokinase. CcpA was also shown to affect lactose metabolism in vivo and to bind to the lacA promoter region in vitro. Collectively, our study reveals complex molecular circuits controlling lactose metabolism in S. mutans, where LacR and CcpA integrate cellular and environmental cues to regulate metabolism of a variety of carbohydrates that are critical to persistence and pathogenicity of S. mutans.     

酵母中葡萄糖阻遏作用机制研究进展

大多数微生物通过一种复杂的机制来感知和传递环境中的葡萄糖变化并对其做出适当的反应。酵母细胞中，葡萄糖主要通过Snf1/Mig1信号通路来阻遏三羧酸循环、糖异生、乙醛酸循环和替代碳源代谢等相关基因的转录表达。木糖、半乳糖、蔗糖、乙醇和有机酸等替代碳源只有当环境中的葡萄糖消耗殆尽后才能重启代谢编程，进行替代碳源的利用。而葡萄糖去抑制对于提高现代微生物工业生产效率、解决环境与能源问题具有重要意义。本文综述了Snf1/Mig1信号通路阻遏机制以及相关转录因子的活性位点，具体介绍了多种替代碳源的应用以及其受葡萄糖阻遏的具体机制，总结提出了根据不同背景缓解或解除碳代谢阻遏的策略，以期为酵母菌现代化生产应用范围的扩大和效率的提高提供新思路。     

The Hox Transcription Factor Ubx Ensures Somatic Myogenesis by Suppressing the Mesodermal Master Regulator Twist

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Two genetic arrangements determining flagellar antigen specificities in two diphasic Escherichia coli strains

Abstract Two diphasic Escherichia coli strains, Bi7327-41 and P12b, which spontaneously change their flagellar antigenic characters from H3 to H16, and from H17 to H4, respectively, were investigated. New features of the genetic control of flagellar phase variation in Bi7327-41 and Salmonella were found. Two genes responsible for the alternative flagellar phases H17 and H4 were demonstrated in P12b. They differed from hagA (H16) and hagB (H3), the two flagellin genes of Bi7327-41, in not being alleles of hagB (H3) or sensitive to the hagA (H16)-specific repressor.     

Histone H3 lysine 27 crotonylation mediates gene transcriptional repression in chromatin

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