An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

In nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The latter state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g. K9ac, K14ac, K18ac) is linked to increased H3K4me3 engagement by the BPTF PHD finger, but it is unknown if this mechanism has a broader extension. Here, we show that H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is not observed on peptide substrates yet occurs on the cis H3 tail, as determined with fully-defined heterotypic nucleosomes. In vivo, H3 tail acetylation is directly and dynamically coupled with cis H3K4 methylation levels. Together, these observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates read-write accessibility in nucleosomes and resolves the long-standing question of why H3K4me3 levels are coupled with H3 acetylation

An Integrated Computational Materials Engineering Predictive Platform for Fatigue Prediction and Qualification of Metallic Parts Built With Additive Manufacturing

Abstract Additive manufacturing (AM) processes create material directly into a functional shape. Often the material properties vary with part geometry, orientation, and build layout. Today, trial-and-error methods are used to generate material property data under controlled conditions that may not map to the entire range of geometries over a part. Described here is the development of a modeling tool enabling prediction of the performance of parts built with AM, with rigorous consideration of the microstructural properties governing the nucleation and propagation of fatigue cracks. This tool, called DigitalClone® for additive manufacturing (DCAM), is an Integrated Computational Materials Engineering (ICME) tool that includes models of crack initiation and damage progression with the high-fidelity process and microstructure modeling approaches. The predictive model has three main modules: process modeling, microstructure modeling, and fatigue modeling. In this paper, a detailed description and theoretical basis of each module is provided. Experimental validations (microstructure, porosity, and fatigue) of the tool using multiple material characterization and experimental coupon testing for five different AM materials are discussed. The physics-based computational modeling encompassed within DCAM provides an efficient capability to fully explore the design space across geometries and materials, leading to components that represent the optimal combination of performance, reliability, and durability.</jats:p

Fabrication of Meter-Scale Laser Resistant Mirrors for the National Ignition Facility, a Fusion Laser

Large-aperture laser-resistant mirrors are required for the construction of the National Ignition Facility, a 1.8 MJ laser. In order to fabricate the 1408 mirrors, a development program was started in 1994 to improve coating quality, manufacturing rate, and lower unit cost. New technologies and metrology tools were scaled to meter size for facilitization in 1999 at Spectra-Physics and the Laboratory of Laser Energetics at the University of Rochester. Pilot production, to fabricate 5-10% of each component, commenced in 2001 and full production rates were achieved in 2002. Coating production will be completed in 2008 with the coating of 460 m{sup 2} of high-damage-threshold precision coatings on 100 tons of BK7 glass with yields exceeding 90%

An acetylation-mediated chromatin switch governs H3K4 methylation read-write capability

ABSTRACTIn nucleosomes, histone N-terminal tails exist in dynamic equilibrium between free/accessible and collapsed/DNA-bound states. The DNA-bound state is expected to impact histone N-termini availability to the epigenetic machinery. Notably, H3 tail acetylation (e.g., K9ac, K14ac, K18ac) is linked to increased engagement of H3K4me3 by the BPTF PHD finger, but it is unknown if this mechanism has broader extension. Here we show that cis H3 tail acetylation promotes nucleosomal accessibility to other H3K4 methyl readers, and importantly, extends to H3K4 writers, notably methyltransferase MLL1. This regulation is nucleosome-dependent and also observed in vivo, where H3 acetylation is directly linked to increased levels of H3K4 methylation on the same histone tail. These observations reveal an acetylation ‘chromatin switch’ on the H3 tail that modulates the accessibility and function of H3K4 methylation in chromatin. Our findings also resolve the long-standing question of why H3K4me3 levels are coupled with H3 acetylation.</jats:p