Actin-Related Protein Arp6 Influences H2A.Z-Dependent and -Independent Gene Expression and Links Ribosomal Protein Genes to Nuclear Pores

Actin-related proteins are ubiquitous components of chromatin remodelers and are conserved from yeast to man. We have examined the role of the budding yeast actin-related protein Arp6 in gene expression, both as a component of the SWR1 complex (SWR-C) and in its absence. We mapped Arp6 binding sites along four yeast chromosomes using chromatin immunoprecipitation from wild-type and swr1 deleted (swr1Δ) cells. We find that a majority of Arp6 binding sites coincide with binding sites of Swr1, the catalytic subunit of SWR-C, and with the histone H2A variant Htz1 (H2A.Z) deposited by SWR-C. However, Arp6 binding detected at centromeres, the promoters of ribosomal protein (RP) genes, and some telomeres is independent of Swr1 and Htz1 deposition. Given that RP genes and telomeres both show association with the nuclear periphery, we monitored the ability of Arp6 to mediate the localization of chromatin to nuclear pores. Arp6 binding is sufficient to shift a randomly positioned locus to nuclear periphery, even in a swr1Δ strain. Arp6 is also necessary for the pore association of its targeted RP promoters possibly through cell cycle-dependent factors. Loss of Arp6, but not Htz1, leads to an up-regulation of these RP genes. In contrast, the pore-association of GAL1 correlates with Htz1 deposition, and loss of Arp6 reduces both GAL1 activation and peripheral localization. We conclude that Arp6 functions both together with the nucleosome remodeler Swr1 and also without it, to mediate Htz1-dependent and Htz1-independent binding of chromatin domains to nuclear pores. This association is shown to have modulating effects on gene expression

Primary hypertension and neurovascular compression: a meta-analysis of magnetic resonance imaging studies.

Item does not contain fulltextOBJECT: Several studies have suggested that neurovascular compression (NVC) of the brainstem might be a cause of hypertension. Because this compression syndrome might be demonstrated by MR imaging studies, several authors have tried to assess its prevalence in small series of patients with hypertension. This article presents a meta-analysis of these studies. METHODS: The studies reviewed by the authors were based on MR imaging and included the presence of left-sided NVC of the left rostral ventrolateral medulla oblongata (RVLM) and/or the cranial nerves IX and X root entry zone in patients with apparent primary hypertension compared with normotensive patients. Several studies also included patients with secondary hypertension as an additional control group, which is analyzed separately. RESULTS: Meta-analysis included data from 14 studies (597 patients with primary hypertension and 609 controls). The effect size was OR 2.68 (95% CI 1.51-4.75, p = 0.001) (random effect), which is consistent with the hypothesis that NVC of the left RVLM is more frequent in patients with apparent primary hypertension compared with normotensive individuals. Stratification for the study design revealed an effect size for prospective studies of OR 1.97 (95% CI 0.74-5.30, p = 0.178) and for retrospective studies of OR 3.36 (95% CI 1.66-6.79, p = 0.001). CONCLUSIONS: This meta-analysis indicates a statistically significant effect size for left-sided NVC in apparent primary hypertension. However, this effect is absent if subanalysis is confined to prospective studies.1 januari 201