mCHH islands are peaks of CHH methylation that occur primarily upstream to genes. These regions are actively targeted by the methylation machinery, occur at boundaries between heterochromatin and euchromatin, and tend to be near highly expressed genes. Here we took an evolutionary perspective by studying upstream mCHH islands across a sample of eight grass species. Using a statistical approach to define mCHH islands as regions that differ from genome-wide background CHH methylation levels, we demonstrated that mCHH islands are common and associate with 39% of genes, on average. We hypothesized that islands should be more frequent in genomes of large size, because they have more heterochromatin and hence more need for defined boundaries. We found, however, that smaller genomes tended to have a higher proportion of genes associated with 5’ mCHH islands. Consistent with previous work suggesting that islands reflect the silencing of the edge of transposable elements (TEs), genes with nearby TEs were more likely to have mCHH islands. However, the presence of mCHH islands was not a function solely of TEs, both because the underlying sequences of islands were often not homologous to TEs and because genic properties also predicted the presence of 5’ mCHH islands. These genic properties included length and gene-body methylation (gbM); in fact, in three of eight species the absence of gbM was a stronger predictor of a 5’ mCHH island than TE proximity. In contrast, gene expression level was a positive but weak predictor of the presence of an island. Finally, we assessed whether mCHH islands were evolutionarily conserved by focusing on a set of 2,720 orthologs across the eight species. They were generally not conserved across evolutionary time. Overall, our data establishes additional genic properties that are associated with mCHH islands and suggests that they are not just a consequence of the TE silencing machinery.
Cystic Fibrosis (CF) is caused by loss of function mutations in the Cystic Fibrosis transmembrane conductance regulator (CFTR). The folding and assembly of CFTR is inefficient. Deletion of F508 in the first nucleotide binding domain (NBD1-ΔF508) further disrupts protein stability leading to endoplasmic reticulum retention and proteasomal degradation. Stabilization and prevention of NBD1-ΔF508 aggregation is critical to rescuing the folding and function of the entire CFTR channel. We report that the phenolic compounds Oleuropein and Hydroxytryosol reduce aggregation of NBD1-ΔF508. The NBD1-ΔF508 aggregate size was smaller in the presence of Hydroxytryosol as determined by dynamic light scattering. Neither phenolic compound increased the thermal stability of NBD1-ΔF508 as measured by differential scanning fluorimetry. Interestingly, Hydroxytyrosol inhibited the stabilizing effect of the indole compound BIA, a known stabilizer, on NBD1-ΔF508. Molecular docking studies predicted that Oleuropein preferred to bind in the F1-type core ATP-binding subdomain in NBD1. In contrast, Hydroxytyrosol preferred to bind in the α4/α5/α6 helical bundle of the ABCα subdomain of NBD1 next to the putative binding site for BIA. This result suggests that Hydroxytyrosol interferes with BIA binding, thus providing an explanation for the antagonistic effect on NBD1 stability upon incubation with both compounds. To our knowledge, these studies are the first to explore the effects of these two phenolic compounds on the aggregation and stability of NBD1-ΔF508 domain of CFTR.
RNA molecules carry information in their primary sequence and also their secondary structure. Secondary structure can confer important functional information, but it is also a potential signal for an RNAi-like host epigenetic response mediated by small interfering RNAs (siRNAs). In this study, we predicted local secondary structures in features of the maize genome, focusing on small regions that had folding energies similar to pre-miRNA loci. We found secondary structures to be common in retrotransposons, inHelitrons, and in genes. These structured regions mapped higher diversities of siRNAs than regions without structure, explaining up to 24% of variation of the siRNA distribution across some TE types. Among genes, those with secondary structure were 1.5-fold more highly expressed, on average, than genes without secondary structure. However, these genes were also more variably expressed across the 26 NAM lines, and this variability correlated with the number of mapping siRNAs. We conclude that local stem-loop structures are a nearly ubiquitous feature of expressed regions of the maize genome, that they correlate with higher siRNA mapping, and that they can represent a trade-off between functional need and the potentially negative consequences of siRNA production.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.