The ammonia oxidation reaction on Pt{ 100) has been investigated over the temperature range 300-800 K, using molecular beams under UHV conditions. The reaction is biphasic, with N2 being the major product below 600 K and NO being the major product above 600 K. It is found that product selectivity can be controlled by varying the beam composition as well as by varying the surface temperature. The efficiency of the reaction to NO can be significantly increased by preadsorption of oxygen on the crystal. Coadsorption and isothermal experiments translate the beam composition dependence into a surface oxygen coverage dependence, with high oxygen coverages resulting in the suppression of N2 production. N2 is believed to be produced mainly from the dissociation of NO produced by oxidation of adsorbed N H 3 . The observed oxygen coverage dependence of product formation is explained by a sharp fall in the heat of adsorption of the dissociated N(a) and O(a) with increasing O(a) coverage. At high surface oxygen coverages the suppression of NZ production arises from the resulting inhibition of NO dissociation. The observed surface temperature dependence of product formation is explained by competition between NO desorption and NO dissociation.

During development, the formation of a mature, well-functioning heart requires transformation of the ventricular wall from a loose trabecular network into a dense compact myocardium at mid-gestation. Failure to compact is associated in humans with congenital diseases such as left ventricular non-compaction (LVNC). The mechanisms regulating myocardial compaction are however still poorly understood. Here, we show that deletion of the Ino80 chromatin remodeler in vascular endothelial cells prevents ventricular compaction in the developing mouse heart. This correlates with defective coronary vascularization, and specific deletion of Ino80 in the two major coronary progenitor tissues-sinus venosus and endocardium-causes intermediate phenotypes. In vitro, endothelial cells promote myocardial expansion independently of blood flow in an Ino80-dependent manner. Ino80 deletion increases the expression of E2F-activated genes and endothelial cell S-phase occupancy. Thus, Ino80 is essential for coronary angiogenesis and allows coronary vessels to support proper compaction of the heart wall.

Highlights d Histone lysine crotonylation (Kcr) oscillates in the yeast metabolic cycle (YMC) d Deregulation of crotonyl-CoA metabolism results in YMC defects d Taf14, a histone Kcr reader, is needed for transcription oscillations in the YMC d Kcr reading by Taf14 reduces growth gene expression during nutrient limitation

The development of many sporadic cancers is directly initiated by carcinogen exposure. Carcinogens induce malignancies by creating DNA lesions (i.e., adducts) that can result in mutations if left unrepaired. Despite this knowledge, there has been remarkably little investigation into the regulation of susceptibility to acquire DNA lesions. In this study, we present the first quantitative human genome-wide map of DNA lesions induced by ultraviolet (UV) radiation, the ubiquitous carcinogen in sunlight that causes skin cancer. Remarkably, the pattern of carcinogen susceptibility across the genome of primary cells significantly reflects mutation frequency in malignant melanoma. Surprisingly, DNase-accessible euchromatin is protected from UV, while lamina-associated heterochromatin at the nuclear periphery is vulnerable. Many cancer driver genes have an intrinsic increase in carcinogen susceptibility, including the oncogene that has the highest mutation frequency in melanoma. These findings provide a genome-wide snapshot of DNA injuries at the earliest stage of carcinogenesis. Furthermore, they identify carcinogen susceptibility as an origin of genome instability that is regulated by nuclear architecture and mirrors mutagenesis in cancer.

d ATP-dependent chromatin remodeling complexes are essential for transcription regulation, and yet it is unclear how these multisubunit complexes coordinate their activities to facilitate diverse transcriptional responses. In this study, we found that the conserved Arp5 and Ies6 subunits of the Saccharomyces cerevisiae INO80 chromatin-remodeler form an abundant and distinct subcomplex in vivo and stimulate INO80-mediated activity in vitro. Moreover, our genomic studies reveal that the relative occupancy of Arp5-Ies6 correlates with nucleosome positioning at transcriptional start sites and expression levels of >1,000 INO80-regulated genes. Notably, these genes are significantly enriched in energy metabolism pathways. Specifically, arp5⌬, ies6⌬, and ino80⌬ mutants demonstrate decreased expression of genes involved in glycolysis and increased expression of genes in the oxidative phosphorylation pathway. Deregulation of these metabolic pathways results in constitutively elevated mitochondrial potential and oxygen consumption. Our results illustrate the dynamic nature of the INO80 complex assembly and demonstrate for the first time that a chromatin remodeler regulates glycolytic and respiratory capacity, thereby maintaining metabolic stability. E ukaryotic genomic DNA is assembled with histones to form chromatin, a complex structure that undergoes constant dynamic reorganization in coordination with DNA-templated processes. Chromatin remodeling, an ATP-dependent mechanism by which nucleosomes are repositioned and reconstructed, is a fundamental component of chromatin manipulation and influences numerous DNA-templated pathways. Because chromatin remodelers are involved in essential cellular processes, defects in remodeling activity directly result in fitness deficiencies in lower eukaryotes, as well as developmental defects and disease in higher eukaryotes (1, 2).In particular, disruption of INO80, an evolutionarily conserved chromatin remodeling complex, results in pluripotency defects and carcinogenesis (3-6). The INO80 complex has demonstrated roles in transcription (7-9), replication (10-12), DNA damage responses (13-16), telomere regulation (17), and mitotic stability (18,19). These studies exemplify the functional diversity of the INO80 complex in different pathways (20). Moreover, they highlight the need for regulatory mechanisms that direct its activity among, and within, these processes.Ample opportunities for regulation of chromatin remodeling exist at the level of individual remodeler complex subunits. For example, different subunits of the INO80 complex are involved in DNA repair and cell cycle checkpoint responses (13, 16). Structural studies demonstrate that these subunits are components of different modules that interact with distinct domains of the S. cerevisiae Ino80 ATPase subunit (21) and thus may impart regulatory functions on ATP-dependent activities of the INO80 complex.For example, a module consisting of actin and actin-related proteins (Arps) Arp8 and Arp4 interacts with the helicase-associated...