A gene-rich, transcriptionally active environment and the pre-deposition of repressive marks are predictive of susceptibility to KRAB/KAP1-mediated silencing.

AbstractBACKGROUND: KRAB-ZFPs (Krüppel-associated box domain-zinc finger proteins) are vertebrate-restricted transcriptional repressors encoded in the hundreds by the mouse and human genomes. They act via an essential cofactor, KAP1, which recruits effectors responsible for the formation of facultative heterochromatin. We have recently shown that KRAB/KAP1 can mediate long-range transcriptional repression through heterochromatin spreading, but also demonstrated that this process is at times countered by endogenous influences.METHOD: To investigate this issue further we used an ectopic KRAB-based repressor. This system allowed us to tether KRAB/KAP1 to hundreds of euchromatic sites within genes, and to record its impact on gene expression. We then correlated this KRAB/KAP1-mediated transcriptional effect to pre-existing genomic and chromatin structures to identify specific characteristics making a gene susceptible to repression.RESULTS: We found that genes that were susceptible to KRAB/KAP1-mediated silencing carried higher levels of repressive histone marks both at the promoter and over the transcribed region than genes that were insensitive. In parallel, we found a high enrichment in euchromatic marks within both the close and more distant environment of these genes.CONCLUSION: Together, these data indicate that high levels of gene activity in the genomic environment and the pre-deposition of repressive histone marks within a gene increase its susceptibility to KRAB/KAP1-mediated repression.

Diversity and Unity of islam in Europe. Some Reflections

(Résumé de l'ouvrage) This volume embodies an uptodate and sensitive set of studies exploring the ongoing negotiation of European Muslim identities in Europe. The Editor argues there has been hitherto a three-fold response on the part of Muslims in Europe (some of whom are now 3rd generation Europeans) - integrationism, isolationism, and escapism. Today the latter two responses are giving way, it is argued, to an active shaping of Muslim European identities. The central issue remains: what degree of freedom and what potential for cultural and religious diversity can minorities have in an outwardly secular and plural European society?

The First Christian Historian. Writing the "Acts of the Apostles"

As the first historian of Christianity, Luke's reliability is vigorously disputed among scholars. The author of the Acts is often accused of being a biased, imprecise, and anti-Jewish historian who created a distorted portrait of Paul. Daniel Marguerat tries to avoid being caught in this true/false quagmire when examining Luke's interpretation of history. Instead he combines different tools - reflection upon historiography, the rules of ancient historians and narrative criticism - to analyse the Acts and gauge the historiographical aims of their author. Marguerat examines the construction of the narrative, the framing of the plot and the characterization, and places his evaluation firmly in the framework of ancient historiography, where history reflects tradition and not documentation. This is a fresh and original approach to the classic themes of Lucan theology: Christianity between Jerusalem and Rome, the image of God, the work of the Spirit, the unity of Luke and the Acts.

Martin Lindhart (Ed.), Practicing the Faith. The Ritual Life of Pentecostal-Charismatic Christians, Berghahn Books, Oxford, 2011, 344 p.

This edited volume examines, from a ritual perspective, Pentecostal-Charismatic groups that are the fastest growing religious movements in the world today. The authors, who are anthropologists, ethnologists or sociologists (with one theologian) collected rich and diverse material on healing, deliverance, personal devotion, public engagement. Their work covers several regions such as Chile, South California, Fiji, Kenya, and Sweden. After an introduction by the editor, eleven chapters examine various issues relevant to the field. Overcoming the diversity of subjects, the unity of the volume is provided by the general ritual perspective and by the methodological implications of employing such a perspective.

Global DNA hypomethylation coupled to repressive chromatin domain formation and gene silencing in breast cancer.

While genetic mutation is a hallmark of cancer, many cancers also acquire epigenetic alterations during tumorigenesis including aberrant DNA hypermethylation of tumor suppressors, as well as changes in chromatin modifications as caused by genetic mutations of the chromatin-modifying machinery. However, the extent of epigenetic alterations in cancer cells has not been fully characterized. Here, we describe complete methylome maps at single nucleotide resolution of a low-passage breast cancer cell line and primary human mammary epithelial cells. We find widespread DNA hypomethylation in the cancer cell, primarily at partially methylated domains (PMDs) in normal breast cells. Unexpectedly, genes within these regions are largely silenced in cancer cells. The loss of DNA methylation in these regions is accompanied by formation of repressive chromatin, with a significant fraction displaying allelic DNA methylation where one allele is DNA methylated while the other allele is occupied by histone modifications H3K9me3 or H3K27me3. Our results show a mutually exclusive relationship between DNA methylation and H3K9me3 or H3K27me3. These results suggest that global DNA hypomethylation in breast cancer is tightly linked to the formation of repressive chromatin domains and gene silencing, thus identifying a potential epigenetic pathway for gene regulation in cancer cells.

Epigenetic regulatory elements associate with specific histone modifications to prevent silencing of telomeric genes.

In eukaryotic cells, transgene expression levels may be limited by an unfavourable chromatin structure at the integration site. Epigenetic regulators are DNA sequences which may protect transgenes from such position effect. We evaluated different epigenetic regulators for their ability to protect transgene expression at telomeres, which are commonly associated to low or inconsistent expression because of their repressive chromatin environment. Although to variable extents, matrix attachment regions (MARs), ubiquitous chromatin opening element (UCOE) and the chicken cHS4 insulator acted as barrier elements, protecting a telomeric-distal transgene from silencing. MARs also increased the probability of silent gene reactivation in time-course experiments. Additionally, all MARs improved the level of expression in non-silenced cells, unlike other elements. MARs were associated to histone marks usually linked to actively expressed genes, especially acetylation of histone H3 and H4, suggesting that they may prevent the spread of silencing chromatin by imposing acetylation marks on nearby nucleosomes. Alternatively, an UCOE was found to act by preventing deposition of repressive chromatin marks. We conclude that epigenetic DNA elements used to enhance and stabilize transgene expression all have specific epigenetic signature that might be at the basis of their mode of action.

Prediction in forensic science: a critical examination of common understandings

In this commentary, we argue that the term 'prediction' is overly used when in fact, referring to foundational writings of de Finetti, the correspondent term should be inference. In particular, we intend (i) to summarize and clarify relevant subject matter on prediction from established statistical theory, and (ii) point out the logic of this understanding with respect practical uses of the term prediction. Written from an interdisciplinary perspective, associating statistics and forensic science as an example, this discussion also connects to related fields such as medical diagnosis and other areas of application where reasoning based on scientific results is practiced in societal relevant contexts. This includes forensic psychology that uses prediction as part of its vocabulary when dealing with matters that arise in the course of legal proceedings.

Luc-Actes: une unité à construire

(Résumé de l'ouvrage) This volume contains the papers presented at the 47th Colloquium Biblicum Lovaniense (Leuven, 1998). The general theme of the meeting was the unity of the Gospel of Luke and the Acts of the Apostles. Main papers on this topic were read by R.L. Brawley, J. Delobel, A. Denaux, J.A. Fitzmeyer, F.W. Horn, J. Kremer, A. Lindemann, O. Mainville, D. Marguerat, F. Neirynck, W. Radl, M. Rese, J. Taylor, C.M. Tuckett, and J. Verheyden. While a large majority of scholars agree that Luke intended his work to cover both the past and the continuing history of Jesus (Gospel and Acts), the essays also illustrate the complexities of this view on the unity of Luke-Acts when it comes to interpret the various aspects of Lukan theology, christology, pneumatology, and ecclesiology, the expansion of the Church in light of its Jewish origins, the genre of Luke-Acts, and the literary and stylistic means Luke used to make his work a unity. In total the volume includes some 40 papers, of which 24 are offered papers: L. Alexander, H. Baarlink, M. Bachmann, D. Bechard, T.L. Brodie, G.P. Carras, A. del Agua, C. Focant, G. Geiger, B.J. Koet, V. Koperski, D.P. Moessner, G. Oegema, J. Pichler, E. Plümacher, A. Puig i Tarrèch, U. Schmid, B. Schwank, N. Taylor, P.J. Tomson, S. Van den Eynde, S. Walton, G. Wasserberg, F. Wilk. This collection is an invaluable contribution to current discussions in Lukan study and to a nuanced understanding of the relationship between Luke's two volumes.

Update on osteoporosis from the 2014 Santa Fe Bone symposium.

The 2014 Santa Fe Bone Symposium provided a setting for the presentation and discussion of the clinical relevance of recent advances in the fields of osteoporosis and metabolic bone disease. The format included oral presentations of abstracts by endocrinology fellows, plenary lectures, panel discussions and breakout sessions, with ample opportunities for informal discussions before and after scheduled events. Topics addressed in these proceedings included a review of the important scientific publications in the past year, fracture prevention in patients with dysmobility and immobility, fracture liaison services for secondary fracture prevention, management of pre-menopausal osteoporosis, the role of bone microarchitecture in determining bone strength, measurement of microarchitecture in clinical practice and methods to improve the quality of bone density testing. This is a report of the proceedings of the 2014 Santa Fe Bone Symposium.