RNA polymerase II clusters form in line with surface condensation on regulatory chromatin

It is essential for cells to control which genes are transcribed into RNA. In eukaryotes, two major control points are recruitment of RNA polymerase II (Pol II) into a paused state, and subsequent pause release toward transcription. Pol II recruitment and pause release occur in association with macromolecular clusters, which were proposed to be formed by a liquid–liquid phase separation mechanism. How such a phase separation mechanism relates to the interaction of Pol II with DNA during recruitment and transcription, however, remains poorly understood. Here, we use live and super-resolution microscopy in zebrafish embryos to reveal Pol II clusters with a large variety of shapes, which can be explained by a theoretical model in which regulatory chromatin regions provide surfaces for liquid-phase condensation at concentrations that are too low for canonical liquid–liquid phase separation. Model simulations and chemical perturbation experiments indicate that recruited Pol II contributes to the formation of these surface-associated condensates, whereas elongating Pol II is excluded from these condensates and thereby drives their unfolding

Damage function for historic paper. Part II: Wear and tear

Background: As a result of use of library and archival documents, defined as reading with handling in the context of general access, mechanical degradation (wear and tear) accumulates. In contrast to chemical degradation of paper, the accumulation of wear and tear is less well studied. Previous work explored the threshold of mechanical degradation at which a paper document is no longer considered to be fit for the purpose of use by a reader, while in this paper we explore the rate of accumulation of such damage in the context of object handling. Results: The degree of polymerisation (DP) of historic paper of European origin from mid-19th–mid-20th Century was shown to affect the rate of accumulation of wear and tear. While at DP > 800, this accumulation no longer depends on the number of handlings (the process is random), a wear-out function could be developed for documents with DP between 300 and 800. For objects with DP < 300, one large missing piece (i.e. such that contains text) developed on average with each instance of handling, which is why we propose this DP value as a threshold value for safe handling. Conclusions: The developed model of accumulation of large missing pieces per number of handlings of a document depending on DP, enables us to calculate the time required for an object to become unfit for use by readers in the context of general access. In the context of the average frequency of document use at The UK National Archives (Kew), this period is 60 years for the category of papers with DP 300, and 450 years for papers with DP 500. At higher DP values, this period of time increases beyond the long-term planning horizon of 500 years, leading to the conclusion that for such papers, accumulation of wear and tear is not a significant collection management concern