Chromosome boundary elements and regulation of heterochromatin spreading

Chromatin is generally classified as euchromatin or heterochromatin, each with distinct histone modifications, compaction levels, and gene expression patterns. Although the proper formation of heterochromatin is essential for maintaining genome integrity and regulating gene expression, heterochromatin can also spread into neighboring regions in a sequence-independent manner, leading to the inactivation of genes. Because the distance of heterochromatin spreading is stochastic, the formation of boundaries, which block the spreading of heterochromatin, is critical for maintaining stable gene expression patterns. Here we review the current understanding of the mechanisms underlying heterochromatin spreading and boundary formation.     

Cholera toxin structure, gene regulation and pathophysiological and immunological aspects

Many notions regarding the function, structure and regulation of cholera toxin expression have remained essentially unaltered in the last 15 years. At the same time, recent findings have generated additional perspectives. For example, the cholera toxin genes are now known to be carried by a non-lytic bacteriophage, a previously unsuspected condition. Understanding of how the expression of cholera toxin genes is controlled by the bacterium at the molecular level has advanced significantly and relationships with cell-density-associated (quorum-sensing) responses have recently been discovered. Regarding the cell intoxication process, the mode of entry and intracellular transport of cholera toxin are becoming clearer. In the immunological field, the strong oral immunogenicity of the non-toxic B subunit of cholera toxin (CTB) has been exploited in the development of a now widely licensed oral cholera vaccine. Additionally, CTB has been shown to induce tolerance against co-administered (linked) foreign antigens in some autoimmune and allergic diseases. Received 25 October 2007; accepted 12 December 2007     

Developmental regulation of p70 S6 kinase by a G protein-coupled receptor dynamically modelized in primary cells

The mechanisms whereby G protein-coupled receptors (GPCR) activate signalling pathways involved in mRNA translation are ill-defined, in contrast to tyrosine kinase receptors (TKR). We compared a GPCR and a TKR, both endogenously expressed, for their ability to mediate phosphorylation of 70-kDa ribosomal S6 kinase p70S6K in primary rat Sertoli cells at two developmental stages. In proliferating cells stimulated with follicle-stimulating hormone (FSH), active p70S6K was phosphorylated on T389 and T421/S424, through cAMP-dependent kinase (PKA) and phosphatidyl-inositide-3 kinase (PI3K) antagonizing actions. In FSH-stimulated differentiating cells, active p70S6K was phosphorylated solely on T389, PKA and PI3K independently enhancing its activity. At both developmental stages, insulin-induced p70S6K regulation was consistent with reported data. Therefore, TKR and GPCR trigger distinct p70S6K active conformations. p70S6K developmental regulation was formalized in a dynamic mathematical model fitting the data, which led to experimentally inaccessible predictions on p70S6K phosphorylation rate.     

Different roles of the human Orc6 protein in the replication initiation process

In eukaryotes, binding of the six-subunit origin recognition complex (ORC) to DNA provides an interactive platform for the sequential assembly of pre-replicative complexes. This process licenses replication origins competent for the subsequent initiation step. Here, we analyze the contribution of human Orc6, the smallest subunit of ORC, to DNA binding and pre-replicative complex formation. We show that Orc6 not only interacts with Orc1–Orc5 but also with the initiation factor Cdc6. Biochemical and imaging experiments reveal that this interaction is required for licensing DNA replication competent. Furthermore, we demonstrate that Orc6 contributes to the interaction of ORC with the chaperone protein HMGA1a (high mobility group protein A1a). Binding of human ORC to replication origins is not specified at the level of DNA sequence and the functional organization of origins is poorly understood. We have identified HMGA1a as one factor that might direct ORC to AT-rich heterochromatic regions. The systematic analysis of the interaction between ORC and HMGA1a revealed that Orc6 interacts with the acidic C-terminus of HMGA1a and also with its AT-hooks. Both domains support autonomous replication if targeted to DNA templates. As such, Orc6 functions at different stages of the replication initiation process. Orc6 can interact with ORC chaperone proteins such as HMGA1a to facilitate chromatin binding of ORC and is also an essential factor for pre-RC formation.     

Parathymische Lymphknoten der Maus und ihre Reaktion auf Thymektomie

Summary The effect of complete and partial, neonatal thymectomy on parathymic lymphnodes was investigated in NMRI-mice. The results indicate that neonatal extirpation of thymic tissue causes an increase in size and number of parathymic lymphnodes.

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Mit Unterstützung der Deutschen Forschungsgemeinschaft.

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Herrn Prof. Dr.O. Westphal zum 60. Geburtstag.     

Isoprotenerol induction of pineal serotonin N-acetyltransferase in normotensive and spontaneously hypertensive rats

Zusammenfassung Verabreichung von Isoprotenerol, eines -adrenergen Agonisten, induziert einen signifikant höheren Anstieg der Aktivität der Serotonin-N-Acetyltransferase in der Epiphyse von spontan hypertensiven, im Vergleich mit normotensiven, Rattenmännchen. Derselbe Unterschied wurde auch bei Weibchen beobachtet, jedoch liegen die Aktivitätswerte bei spontan hypertensiven Männchen allgemein höher. Die durch Isoprotenerol erhöhte Induktion der Serotonin-N-Acetyltransferase erzeugt hinsichtlich der Catecholamine in den Pinealozyten von spontan hypertensiven Ratten eine veränderte Reaktivität der Achse -Rezeptor-Adenylzyklasesystem-Serotonin-N-Acetyl transferase.     

Radioimmunoassay of some hormones simultaneously measured in serum and breast cyst fluid

Summary Blood and breast cyst fluid were drawn simultaneously for hormonal determination. There was no difference between serum and cyst fluid values of PRL and TSH. A significant difference was noted for LH (p<0.01) and FSH (p<0.05), serum concentrations being higher than cyst fluid concentrations.The authors are indebted to Miss J. Meister, E. Dullaert and J. Beck for their skillful technical help. We are also indebted to the National Institutes of Health, NIAMDD and the World Health Organization, International Laboratory for Biological Standards.