67 research outputs found

    A Cell Cycle Role for the Epigenetic Factor CTCF-L/BORIS

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    CTCF is a ubiquitous epigenetic regulator that has been proposed as a master keeper of chromatin organisation. CTCF-like, or BORIS, is thought to antagonise CTCF and has been found in normal testis, ovary and a large variety of tumour cells. The cellular function of BORIS remains intriguing although it might be involved in developmental reprogramming of gene expression patterns. We here unravel the expression of CTCF and BORIS proteins throughout human epidermis. While CTCF is widely distributed within the nucleus, BORIS is confined to the nucleolus and other euchromatin domains. Nascent RNA experiments in primary keratinocytes revealed that endogenous BORIS is present in active transcription sites. Interestingly, BORIS also localises to interphase centrosomes suggesting a role in the cell cycle. Blocking the cell cycle at S phase or mitosis, or causing DNA damage, produced a striking accumulation of BORIS. Consistently, ectopic expression of wild type or GFP- BORIS provoked a higher rate of S phase cells as well as genomic instability by mitosis failure. Furthermore, downregulation of endogenous BORIS by specific shRNAs inhibited both RNA transcription and cell cycle progression. The results altogether suggest a role for BORIS in coordinating S phase events with mitosis

    In Vivo Expression of MHC Class I Genes Depends on the Presence of a Downstream Barrier Element

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    Regulation of MHC class I gene expression is critical to achieve proper immune surveillance. In this work, we identify elements downstream of the MHC class I promoter that are necessary for appropriate in vivo regulation: a novel barrier element that protects the MHC class I gene from silencing and elements within the first two introns that contribute to tissue specific transcription. The barrier element is located in intergenic sequences 3′ to the polyA addition site. It is necessary for stable expression in vivo, but has no effect in transient transfection assays. Accordingly, in both transgenic mice and stably transfected cell lines, truncation of the barrier resulted in transcriptional gene silencing, increased nucleosomal density and decreased histone H3K9/K14 acetylation and H3K4 di-methylation across the gene. Significantly, distinct sequences within the barrier element govern anti-silencing and chromatin modifications. Thus, this novel barrier element functions to maintain transcriptionally permissive chromatin organization and prevent transcriptional silencing of the MHC class I gene, ensuring it is poised to respond to immune signaling

    Development of a kinetic metabolic model: application to Catharanthus roseus hairy root

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    A kinetic metabolic model describing Catharanthus roseus hairy root growth and nutrition was developed. The metabolic network includes glycolysis, pentose-phosphate pathway, TCA cycle and the catabolic reactions leading to cell building blocks such as amino acids, organic acids, organic phosphates, lipids and structural hexoses. The central primary metabolic network was taken at pseudo-steady state and metabolic flux analysis technique allowed reducing from 31 metabolic fluxes to 20 independent pathways. Hairy root specific growth rate was described as a function of intracellular concentration in cell building blocks. Intracellular transport and accumulation kinetics for major nutrients were included. The model uses intracellular nutrients as well as energy shuttles to describe metabolic regulation. Model calibration was performed using experimental data obtained from batch and medium exchange liquid cultures of C. roseus hairy root using a minimal medium in Petri dish. The model is efficient in estimating the growth rate

    Contribution of discourse and morphosyntax skills to reading comprehension in Chinese dyslexic and typically developing children

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    This study aimed at identifying important skills for reading comprehension in Chinese dyslexic children and their typically developing counterparts matched on age (CA controls) or reading level (RL controls). The children were assessed on Chinese reading comprehension, cognitive, and reading-related skills. Results showed that the dyslexic children performed significantly less well than the CA controls but similarly to RL controls in most measures. Results of multiple regression analyses showed that word-level reading-related skills like oral vocabulary and word semantics were found to be strong predictors of reading comprehension among typically developing junior graders and dyslexic readers of senior grades, whereas morphosyntax, a text-level skill, was most predictive for typically developing senior graders. It was concluded that discourse and morphosyntax skills are particularly important for reading comprehension in the non-inflectional and topic-prominent Chinese system

    The alarm call system of female Campbell's monkeys

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    Field studies on male forest guenon alarm-calling behaviour have revealed a number of intricacies about how these primates use vocalizations to protect themselves from predation. In these species, the vocal behaviour of adult females is often different from that of the males, but little systematic work has been done. Here, we describe the alarm call system of female Campbell's monkeys, Cercopithecus campbelli, in their natural forest habitat in western Ivory Coast. We found that in response to disturbing events, females produced three basic alarm call types, 'wak-oos', 'hoks' and acoustically variable 'trill' calls, consisting of repeated and rapidly ascending (RRA) pulses, which varied systematically in the temporal and frequency domains. Using observational and experimental data we were able to demonstrate that the RRA calls consisted of four acoustic variants, which could be associated with specific contexts, allowing listeners to draw inferences about the type of disturbance experienced by the caller. We also compared the alarm call behaviour of free-ranging individuals with published results from captivity. As predicted, captive individuals failed to produce predator-specific alarm calls, but they also produced an RRA variant in response to humans that was absent in the wild. We discuss the relevance of these findings in terms of their broader potential impact on evolutionary theories of primate communication. (C) 2009 The Association for the Study of Animal Behaviour. Published by Elsevier Ltd. All rights reserved.</p
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