Transcription factor LSF facilitiates lysine methylation of α-tubulin by microtubule-associated SET8

Microtubules are critical for mitosis, cell motility, and protein and organelle transport, and are a validated target for anticancer drugs. However, tubulin regulation and recruitment in these cellular processes is less understood. Post-translational modifications of tubulin are proposed to regulate microtubule functions and dynamics. Although many such modifications have been investigated, tubulin methylations and enzymes responsible for methylation have only recently begun to be described. Here we report that N-lysine methyl transferase KMT5A (SET8/PR-Set7), which methylates histone H4K20, also methylates α-tubulin. Furthermore, the transcription factor LSF binds both tubulin and SET8, and enhances α-tubulin methylation in vitro, countered by FQI1, a specific small molecule inhibitor of LSF. Thus, the three proteins SET8, LSF, and tubulin, all essential for mitotic progression, interact with each other. Overall, these results point to dual functions for both SET8 and LSF not only in chromatin regulation, but also for cytoskeletal modification.First author draf

Viking Age garden plants from southern Scandinavia: diversity, taphonomy and cultural aspects

Plant finds recovered from archaeological sites in southern Scandinavia dated to the Viking Age reflect the diversity of useful plants that were cultivated and collected. This review presents the results of 14 investigations of deposits that are dated between AD 775 and 1050. The site types are categorized as agrarian, urban, military and burials. Garden plants are unevenly distributed, as the greatest diversity is recorded in features from urban contexts. We argue that taphonomic processes played an important role in the picture displayed. Archaeobotanical research results from neighbouring regions suggest that Viking Age horticulture has its roots in older traditions, and that the spectrum of garden plants is influenced by central and north-western European horticultural customs, which were to a great extent shaped by Roman occupation

Burden of mortality in Greenland--today and tomorrow.

OBJECTIVES: Investigation of the relative impact of three factors expected to influence the future mortality burden in Greenland: demographic change, epidemiological transition and behavioural patterns. STUDY DESIGN: To identify general trends in public health status, evaluating the effect of public health campaigns and providing the basis for making predictions of future trends in the mortality burden data from the Greenlandic Death Causes Register to estimate Years of Life Lost (YLL) in the period 1976-1998 has been used. METHODS: YLL were estimated according to the Burden of Disease Method. Age standardised death rates were calculated per 10,000 person years. Regression analysis (ordinary least squares) using time as the explanatory variable was applied to project the time series 1976-1998 into the prediction period 1999-2028. RESULTS: The projections indicate that the demographic component in combination with behavioural patterns will have a dominant effect in the expected increase in the future burden of mortality. Relative to these two components, epidemiological transition will constitute a relatively insignificant impact on the future mortality burden in Greenland. CONCLUSION: Concerted multi-sectoral approaches and broad holistic health strategies related to health promotion and prevention today will strategically improve the capability of the Greenlandic society to manage the future disease burden from ageing via its health care sector and the institutional sector for care of the elderly

Hyperinsulinaemic hypoglycaemia - a diagnostic challenge. A report of two atypical cases

Objectives: The authors describe 2 atypical cases of patients with hypoglycaemia, suspected for insulinoma. Methods: The 2 reports are accompanied by a concise review of the literature. Results: Patient 1 had a distal pancreatectomy performed for suspected insulinoma, and was diagnosed with a glucagonoma and beta-cell hyperplasia (nesidioblastosis). To the authors’s knowledge, co-existing glucagonoma and nesidioblastosis had not been previously reported. Patient 2 was diagnosed with a benign insulinoma and 5 years later with metastatic disease. Conclusion: The authors conclude that insulinomas are rare entities which often present a diagnostic and therapeutic challenge. In such cases, patient referral to tertiary multidisciplinary centers is recommended

Transcription factor LSF-DNMT1 complex dissociation by FQI1 leads to aberrant DNA methylation and gene expression

The transcription factor LSF is highly expressed in hepatocellular carcinoma (HCC) and promotes oncogenesis. Factor quinolinone inhibitor 1 (FQI1), inhibits LSF DNA-binding activity and exerts anti-proliferative activity. Here, we show that LSF binds directly to the maintenance DNA (cytosine-5) methyltransferase 1 (DNMT1) and its accessory protein UHRF1 both in vivo and in vitro. Binding of LSF to DNMT1 stimulated DNMT1 activity and FQI1 negated the methyltransferase activation. Addition of FQI1 to the cell culture disrupted LSF bound DNMT1 and UHRF1 complexes, resulting in global aberrant CpG methylation. Differentially methylated regions (DMR) containing at least 3 CpGs, were significantly altered by FQI1 compared to control cells. The DMRs were mostly concentrated in CpG islands, proximal to transcription start sites, and in introns and known genes. These DMRs represented both hypo and hypermethylation, correlating with altered gene expression. FQI1 treatment elicits a cascade of effects promoting altered cell cycle progression. These findings demonstrate a novel mechanism of FQI1 mediated alteration of the epigenome by DNMT1-LSF complex disruption, leading to aberrant DNA methylation and gene expression.We would like to thank Drs. Donald Comb, Rich Roberts, William Jack and Clotilde Carlow at New England Biolabs Inc. for research support and encouragement. The authors thank Dr. Lauren Brown (Boston University Center for Molecular Discovery) for the preparation of FQI1. UH research on this project was supported by Ignition Awards from Boston University and a Johnson & Johnson Clinical Innovator's Award through Boston University. SES research is supported by the NIH (P50 GM067041 & R24 GM111625). Research performed by HGC was partly a requirement for the MCBB graduate program at Boston University and supported by NEB. (Boston University; Johnson & Johnson Clinical Innovator's Award through Boston University; P50 GM067041 - NIH; R24 GM111625 - NIH; NEB)Published versio

Reviews

Reviews: Arne Skjølsvold: Slettabøboplassen. Et bidrag til diskusjonen om forholdet mellem fangst- og bondesamfunnet i yngre steinalder og bronsealder. Stavanger 1977. (by Svend Nielsen). Klaus Ebbesen: Tragtbægerkultur i Nordjylland. Nordiske Fortidsminder. Ser. B, Vol. 5, 197 8. (by P. 0. Nielsen). Birgitta Hulthen: On Ceramic Technology during the Scanian Neolithic and Bronze Age. Stockholm 1977. (by Ulla Engberg). Renate Rolle: Totenkult der Skythen I. Das Steppengebiet. Vorgeschichtliche Forschungen 18,I, I and I,2. Berlin-N.Y. 1979. (by Ole Klindt-Jensen). Werner Haarnagel: Die Grabung Feddersen Wierde. Methode, Hausbau, Siedlungs- u. Wirtschaftsformen sowie Sozialstruktur. Wiesbaden 1979. (by Steen Hvass). U. Nasman and E. Wegraeus (eds.): Eketorp. Fortification and Settlement on Öland/Sweden. The Setting. Stockholm 1979. (by Ulla Lund Hansen). Ingrid Ulbricht: Die Geweihverarbeitung in Haithabu. Die Ausgrabungen in Haithabu, Vol. 7. Neumünster 1978 . Heid Gjöstein Resi: Die Specksteinfunde aus Haithabu. Berichte über die Ausgrabungen in Haithabu, Vol. 14. Neumünster 1979. (by Hans Jørgen Madsen)