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Summary: Metazoan genomes are partitioned into modular chromosomal domains containing active or repressive chromatin. In flies, Polycomb group (PcG) response elements (PREs) recruit PHO and other DNA-binding factors and act as nucleation sites for the formation of Polycomb repressive domains. The sequence specificity of PREs is not well understood. Here, we use comparative epigenomics and transgenic assays to show that Drosophila domain organization and PRE specification are evolutionarily conserved despite significant cis-element divergence within Polycomb domains, whereas cis-element evolution is strongly correlated with transcription factor binding divergence outside of Polycomb domains. Cooperative interactions of PcG complexes and their recruiting factor PHO stabilize PHO recruitment to low-specificity sequences. Consistently, PHO recruitment to sites within Polycomb domains is stabilized by PRC1. These data suggest that cooperative rather than hierarchical interactions among low-affinity sequences, DNA-binding factors, and the Polycomb machinery are giving rise to specific and strongly conserved 3D structures in Drosophila. : Schuettengruber et al. present an extensive comparative epigenomics data set, providing new insights into cis-driven versus buffered evolution of Polycomb recruitment and Polycomb domain specificity. Using chromatin immunoprecipitation sequencing and transgenic assays, they demonstrate an extremely high conservation of Polycomb repressive domains in five Drosophila species. Using Hi-C and knockout experiments, they challenge the standard hierarchical Polycomb recruitment model and demonstrate that cooperative rather than hierarchical interactions among DNA motifs, transcription factors, and Polycomb group complexes define Polycomb domains.

Background: Thromboprophylaxis for hospitalized patients with a high risk of venous thromboembolic events (VTEs) is strongly recommended but is not universally applied on medical units. Outside of randomized trials, there is minimal evidence that the usual medications reduce the incidence of clinically significant VTE., Methods: We conducted a retrospective cohort study including all patients admitted into a teaching medical unit during years 2001-2002, 2003-2004, 2005-2006, 2007-2008 and 2009-2010. Inclusion criteria for the analysis were having one or more risk factors for a VTE and no contraindication to thromboprophylaxis., Results: Of 2,369 patients reviewed, 1,302 satisfied the inclusion criteria. Between years 2001-2002 and 2009-2010, the proportion of patients receiving thromboprophylaxis increased from 29.2% to 76.4% (P < 0.0001) and the duration of thromboprophylaxis increased from 63% of hospital stay to 84% (P = 0.004). There was no statistically significant association between the number of risk factors and the rate of thromboprophylaxis. Overall, only 32 patients suffered from a VTE with no decrease in VTE incidence between years 2001-2002 and 2009-2010. A total of 107 patients had a bleeding event, and there was no statistically significant change in the incidence of bleeding during our study period., Conclusions: In our medical units, we found a statistically significant increase in the use of the thromboprophylaxis practice. However, this was not associated with any statistically significant impact on the VTE incidence. This suggests that patients given thromboprophylaxis could be better selected.