Structural insights into histone exchange by human SRCAP complex

Abstract Histone variant H2A.Z is found at promoters and regulates transcription. The ATP-dependent chromatin remodeler SRCAP complex (SRCAP-C) promotes the replacement of canonical histone H2A–H2B dimer with H2A.Z–H2B dimer. Here, we determined structures of human SRCAP-C bound to H2A-containing nucleosome at near-atomic resolution. The SRCAP subunit integrates a 6-subunit actin-related protein (ARP) module and an ATPase-containing motor module. The ATPase-associated ARP module encircles half of the nucleosome along the DNA and may restrain net DNA translocation, a unique feature of SRCAP-C. The motor module adopts distinct nucleosome binding modes in the apo (nucleotide-free), ADP-bound, and ADP-BeFx-bound states, suggesting that ATPase-driven movement destabilizes H2A–H2B by unwrapping the entry DNA and pulls H2A–H2B out of nucleosome through the ZNHIT1 subunit. Structure-guided chromatin immunoprecipitation sequencing analysis confirmed the requirement of H2A-contacting ZNHIT1 in maintaining H2A.Z occupancy on the genome. Our study provides structural insights into the mechanism of H2A-H2A.Z exchange mediated by SRCAP-C

Effects of Various Marine Toxins on the Mouse Intestine Organoid Model

Because of their trace existence, exquisite structure and unique role, highly toxic marine biotoxins have always led to the development of natural product identification, structure and function research, chemistry and biosynthesis, and there are still many deficiencies in the injury and protection of highly toxic organisms, toxin biosynthesis, rapid detection, poisoning and diagnosis and treatment. In this study, a mouse intestine organoid (MIO) model was constructed to explore the effects of the marine toxins okadaic acid (OA) and conotoxin (CgTx) on MIO. The results showed that the cell mortality caused by the two toxins at middle and high concentrations was significantly higher than the cell mortality of the control group, the ATPase activity in each group exposed to OA was significantly lower than the ATPase activity of the control group, all the CgTx groups were significantly higher than that of the control group, and the number of apoptotic cells was not significantly higher than the number of apoptotic cells of the control group. Through RNA-Seq differential genes, Gene Ontology (GO) and pathway analysis, and Gene Set Enrichment Analysis (GSEA) experimental results, it was demonstrated that OA reduced cell metabolism and energy production by affecting cell transcription in MIO. Ultimately, cell death resulted. In contrast, CgTx upregulated the intracellular hormone metabolism pathway by affecting the nuclear receptor pathway of MIO, which resulted in cell death and the generation of energy in large amounts

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Crystallographic Origin of Phase Transformation and Lamellar Orientation Control for TiAl-Based Alloys

TiAl intermetallics are typical metallic materials involving complex solid-state phase transformations, with crystal orientations that are difficult to control due to multi-transformation variants. However, lamellar orientation control is crucial to the development of a polysynthetic twinned single crystal structure in TiAl-based alloys for jet engines or other high-temperature systems. In this study, β-solidifying TiAl alloys were used to study the relationships between the lamellar structure and the phase transformation process under directional solidification (referred to as the directional phase transformation, DPT). It was found that the β → α phase transition affects the lamellar orientations and that the subsequent process of α → α2 + γ leads to the final formation of the polysynthetic lamellar structure. Detailed analyses based on crystallography show that the β/α phase interface is responsible for the different oriented lamellar structures with the 0° or 45° orientation. With a lower interfacial energy, the 0° oriented α phase nucleates more easily but grows much more slowly than the 45° oriented α phases during DPT, which makes it feasible to control the lamellar orientations for TiAl-based alloys. The crystallographic origin for the control of lamellar orientations was then studied and confirmed by using EBSD in a β-solidifying Ti–Al–Nb alloy