Ruler elements in chromatin remodelers set nucleosome array spacing and phasing

Arrays of regularly spaced nucleosomes dominate chromatin and are often phased by alignment to reference sites like active promoters. How the distances between nucleosomes (spacing), and between phasing sites and nucleosomes are determined remains unclear, and specifically, how ATP-dependent chromatin remodelers impact these features. Here, we used genome-wide reconstitution to probe how Saccharomyces cerevisiae ATP-dependent remodelers generate phased arrays of regularly spaced nucleosomes. We find that remodelers bear a functional element named the ‘ruler’ that determines spacing and phasing in a remodeler-specific way. We use structure-based mutagenesis to identify and tune the ruler element residing in the Nhp10 and Arp8 modules of the INO80 remodeler complex. Generally, we propose that a remodeler ruler regulates nucleosome sliding direction bias in response to (epi)genetic information. This finally conceptualizes how remodeler-mediated nucleosome dynamics determine stable steady-state nucleosome positioning relative to other nucleosomes, DNA bound factors, DNA ends and DNA sequence elements

Advances on the structure of the R2TP/Prefoldin-like complex

Cellular stability, assembly and activation of a growing list of macromolecular complexes require the action of HSP90 working in concert with the R2TP/Prefoldin-like (R2TP/PFDL) co-chaperone. RNA polymerase II, snoRNPs and complexes of PI3-kinase-like kinases, a family that includes the ATM, ATR, DNA-PKcs, TRAPP, SMG1 and mTOR proteins, are among the clients of the HSP90-R2TP system. Evidence links the R2TP/PFDL pathway with cancer, most likely because of the essential role in pathways commonly deregulated in cancer. R2TP forms the core of the co-cochaperone and orchestrates the recruitment of HSP90 and clients, whereas prefoldin and additional prefoldin-like proteins, including URI, associate with R2TP, but their function is still unclear. The mechanism by which R2TP/PFLD facilitates assembly and activation of such a variety of macromolecular complexes is poorly understood. Recent efforts in the structural characterization of R2TP have started to provide some mechanistic insights. We summarize recent structural findings, particularly how cryo-electron microscopy (cryo-EM) is contributing to our understanding of the architecture of the R2TP core complex. Structural differences discovered between yeast and human R2TP reveal unanticipated complexities of the metazoan R2TP complex, and opens new and interesting questions about how R2TP/PFLD works

Heterochromatin and the molecular mechanisms of 'parent-of-origin' effects in animals.

Twenty five years ago it was proposed that conserved components of constitutive heterochromatin assemble heterochromatinlike complexes in euchromatin and this could provide a general mechanism for regulating heritable (cell-to-cell) changes in gene expressibility. As a special case, differences in the assembly of heterochromatin-like complexes on homologous chromosomes might also regulate the parent-of-origin-dependent gene expression observed in placental mammals. Here, the progress made in the intervening period with emphasis on the role of heterochromatin and heterochromatin-like complexes in parent-of-origin effects in animals is reviewed

Polycyclische aromatische Kohlenwasserstoffe in Boeden und Pflanzen. Ein Beitrag zur Gefaehrdungsabschaetzung bei Altlasten. Bd. 1 Untersuchungsverfahren

The assessment of environmental hazards emanating from a group of pollutants presupposes, inter alia, knowledge of their quantities. To establish these requires a reliable analytical method for the qualitative and quantitative determination of the groups of organic pollutants to be investigated. In the case of polycyclic aromatic hydrocarbons the task set was to develop methods permitting to reliably determine PAH concentrations in soil and plants routinely. (orig.)Die Abschaetzung der von einer Schadstoffgruppe ausgehenden Umweltgefaehrdung setzt u.a. die Kenntnis der vorhandenen Mengen voraus. Ihre Ermittlung erfordert ein zuverlaessiges analytisches Verfahren zur qualitativen und quantitativen Bestimmung der jeweils interessierenden Gruppe organischer Schadstoffe. Im Falle der polycyclischen aromatischen Kohlenwasserstoffe galt es, Methoden zu entwickeln, die es im Routineeinsatz gestatten, zuverlaessig die PAK-Konzentrationen in Boeden und Pflanzen zu ermitteln. (orig.)Available from TIB Hannover: RA 8195(41) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEDEGerman