TRIM24 links a non-canonical histone signature to breast cancer

Recognition of modified histone species by distinct structural domains within 'reader' proteins plays a critical role in the regulation of gene expression. Readers that simultaneously recognize histones with multiple marks allow transduction of complex chromatin modification patterns into specific biological outcomes. Here we report that chromatin regulator tripartite motif-containing 24 (TRIM24) functions in humans as a reader of dual histone marks by means of tandem plant homeodomain (PHD) and bromodomain (Bromo) regions. The three-dimensional structure of the PHD-Bromo region of TRIM24 revealed a single functional unit for combinatorial recognition of unmodified H3K4 (that is, histone H3 unmodified at lysine 4, H3K4me0) and acetylated H3K23 (histone H3 acetylated at lysine 23, H3K23ac) within the same histone tail. TRIM24 binds chromatin and oestrogen receptor to activate oestrogen-dependent genes associated with cellular proliferation and tumour development. Aberrant expression of TRIM24 negatively correlates with survival of breast cancer patients. The PHD-Bromo of TRIM24 provides a structural rationale for chromatin activation through a non-canonical histone signature, establishing a new route by which chromatin readers may influence cancer pathogenesis.     

Mechanical properties and microstructure of composites produced by recycling metal chips

In this study, the processing and mechanical properties of porous metal matrix composites (MMCs) composed of spheroidal cast iron chips (GGG40) and bronze chips (CuSn10) and formed by hot isostatic pressing were investigated. Bronze chips (CuSn10) were used as a matrix component, and spheroidal cast iron (GGG40) chips were used as a reinforcement component. The MMCs were produced with different CuSn10 contents (90wt%, 80wt%, 70wt%, and 60wt%). The hot isostatic pressing process was performed under three different pressures and temperatures. The produced MMCs were characterized using density tests, Brinell hardness tests, and compression tests. In addition, the consolidation mechanism was investigated by X-ray diffraction (XRD) analysis and scanning electron microscopy. The test results were compared with those for bulk CuSn10 and bulk GGG40. Mechanical tests results revealed that the metallic chips can be recycled by using hot pressing and that the mechanical properties of the produced MMCs were similar to those of bulk CuSn10. XRD and microscopy studies showed that no intermetallic compounds formed between the metallic chips. The results showed that the CuSn10 and GGG40 chips were consolidated by mechanical interlocking.