Cell cycle–dependent localization of macroH2A in chromatin of the inactive X chromosome

One of several features acquired by chromatin of the inactive X chromosome (Xi) is enrichment for the core histone H2A variant macroH2A within a distinct nuclear structure referred to as a macrochromatin body (MCB). In addition to localizing to the MCB, macroH2A accumulates at a perinuclear structure centered at the centrosome. To better understand the association of macroH2A1 with the centrosome and the formation of an MCB, we investigated the distribution of macroH2A1 throughout the somatic cell cycle. Unlike Xi-specific RNA, which associates with the Xi throughout interphase, the appearance of an MCB is predominantly a feature of S phase. Although the MCB dissipates during late S phase and G2 before reforming in late G1, macroH2A1 remains associated during mitosis with specific regions of the Xi, including at the X inactivation center. This association yields a distinct macroH2A banding pattern that overlaps with the site of histone H3 lysine-4 methylation centered at the DXZ4 locus in Xq24. The centrosomal pool of macroH2A1 accumulates in the presence of an inhibitor of the 20S proteasome. Therefore, targeting of macroH2A1 to the centrosome is likely part of a degradation pathway, a mechanism common to a variety of other chromatin proteins

Proanthocyanidins Modulate MicroRNA Expression in Human HepG2 Cells

Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the post-transcriptional level. These RNAs have been shown to be involved in a several biological processes, human diseases and metabolic disorders. Proanthocyanidins, which are the most abundant polyphenol class in the human diet, have positive health effects on a variety of metabolic disorders such as inflammation, obesity, diabetes and insulin resistance. The present study aimed to evaluate whether proanthocyanidin-rich natural extracts modulate miRNA expression. Using microarray analysis and Q-PCR, we investigated miRNA expression in HepG2 cells treated with proanthocyanidins. Our results showed that when HepG2 cells were treated with grape seed proanthocyanidin extract (GSPE), cocoa proanthocyanidin extract (CPE) or pure epigallocatechin gallate isolated from green tea (EGCG), fifteen, six and five differentially expressed miRNAs, respectively, were identified out of 904 mRNAs. Specifically, miR-30b* was downregulated by the three treatments, and treatment with GSPE or CPE upregulated miR-1224-3p, miR-197 and miR-532-3p. Therefore, these results provide evidence of the capacity of dietary proanthocyanidins to influence microRNA expression, suggesting a new mechanism of action of proanthocyanidins

Regulation of DCC Localization by HTZ-1/H2A.Z and DPY-30 Does not Correlate with H3K4 Methylation Levels

Dosage compensation is a specialized form of gene regulation that balances sex-chromosome linked gene expression between the sexes. In C. elegans, dosage compensation is achieved by the activity of the dosage compensation complex (DCC). The DCC binds along both X chromosomes in hermaphrodites to down-regulate gene expression by half, limiting X-linked gene products to levels produced in XO males. Sequence motifs enriched on the X chromosome play an important role in targeting the DCC to the X. However, these motifs are not strictly X-specific and therefore other factors, such as the chromatin environment of the X chromosome, are likely to aid in DCC targeting. Previously, we found that loss of HTZ-1 results in partial disruption of dosage compensation localization to the X chromosomes. We wanted to know whether other chromatin components coordinated with HTZ-1 to regulate DCC localization. One candidate is DPY-30, a protein known to play a role in DCC localization. DPY-30 homologs in yeast, flies, and mammals are highly conserved members of histone H3 lysine 4 (H3K4) methyltransferase Set1/MLL complexes. Therefore, we investigated the hypothesis that the dosage compensation function of DPY-30 involves H3K4 methylation. We found that in dpy-30 animals the DCC fails to stably bind chromatin. Interestingly, of all the C. elegans homologs of Set1/MLL complex subunits, only DPY-30 is required for stable DCC binding to chromatin. Additionally, loss of H3K4 methylation does not enhance DCC mislocalization in htz-1 animals. We conclude that DPY-30 and HTZ-1 have unique functions in DCC localization, both of which are largely independent of H3K4 methylation

The insulator factor CTCF controls MHC class II gene expression and is required for the formation of long-distance chromatin interactions

Knockdown of the insulator factor CCCTC binding factor (CTCF), which binds XL9, an intergenic element located between HLA-DRB1 and HLA-DQA1, was found to diminish expression of these genes. The mechanism involved interactions between CTCF and class II transactivator (CIITA), the master regulator of major histocompatibility complex class II (MHC-II) gene expression, and the formation of long-distance chromatin loops between XL9 and the proximal promoter regions of these MHC-II genes. The interactions were inducible and dependent on the activity of CIITA, regulatory factor X, and CTCF. RNA fluorescence in situ hybridizations show that both genes can be expressed simultaneously from the same chromosome. Collectively, the results suggest a model whereby both HLA-DRB1 and HLA-DQA1 loci can interact simultaneously with XL9, and describe a new regulatory mechanism for these MHC-II genes involving the alteration of the general chromatin conformation of the region and their regulation by CTCF

Combined effects of heat waves and droughts on avian communities across the conterminous United States

Increasing surface temperatures and climatic variability associated with global climate change are expected to produce more frequent and intense heat waves and droughts in many parts of the world. Our goal was to elucidate the fundamental, but poorly understood, effects of these extreme weather events on avian communities across the conterminous United States. Specifically, we explored: (1) the effects of timing and duration of heat and drought events, (2) the effects of jointly occurring drought and heat waves relative to these events occurring in isolation, and (3) how effects vary among functional groups related to nest location and migratory habit, and among ecoregions with differing precipitation and temperature regimes. Using data from remote sensing, meteorological stations, and the North American Breeding Bird Survey, we used mixed effects models to quantify responses of overall and functional group abundance to heat waves and droughts (occurring alone or in concert) at two key periods in the annual cycle of birds: breeding and post-fledging. We also compared responses among species with different migratory and nesting characteristics, and among 17 ecoregions of the conterminous United States. We found large changes in avian abundances related to 100-year extreme weather events occurring in both breeding and post-fledging periods, but little support for an interaction among time periods. We also found that jointly-, rather than individually-occurring heat waves and droughts were both more common and more predictive of abundance changes. Declining abundance was the only significant response to post-fledging events, while responses to breeding period events were larger but could be positive or negative. Negative responses were especially frequent in the western U.S., and among ground-nesting birds and Neotropical migrants, with the largest single-season declines (36%) occurring among ground-nesting birds in the desert Southwest. These results indicate the importance of functional traits, timing, and geography in determining avian responses to weather extremes. Because dispersal to other regions appears to be an important avian response, it may be essential to maintain habitat refugia in a more climatically variable future

Effects of drought on avian community structure

Droughts are expected to become more frequent under global climate change. Avifauna depend on precipitation for hydration, cover, and food. While there are indications that avian communities respond negatively to drought, little is known about the response of birds with differing functional and behavioral traits, what time periods and indicators of drought are most relevant, or how response varies geographically at broad spatial scales. Our goals were thus to determine (1) how avian abundance and species richness are related to drought, (2) whether community variations are more related to vegetation vigor or precipitation deviations and at what time periods relationships were strongest, (3) how response varies among avian guilds, and (4) how response varies among ecoregions with different precipitation regimes. Using mixed effect models and 1989–2005 North American Breeding Bird Survey data over the central United States, we examined the response to 10 precipitation- and greenness based metrics by abundance and species richness of the avian community overall, and of four behavioral guilds. Drought was associated with the most negative impacts on avifauna in the semiarid Great Plains, while positive responses were observed in montane areas. Our models predict that in the plains, Neotropical migrants respond the most negatively to extreme drought, decreasing by 13.2% and 6.0% in abundance and richness, while permanent resident abundance and richness increase by 11.5% and 3.6%, respectively in montane areas. In most cases, response of abundance was greater than richness and models based on precipitation metrics spanning 32-week time periods were more supported than those covering shorter time periods and those based on greenness. While drought is but one of myriad environmental variations birds encounter, our results indicate that drought is capable of imposing sizable shifts in abundance, richness, and composition on avian communities, an important implication of a more climatically variable future

Experimental river delta size set by multiple floods and backwater hydrodynamics

River deltas worldwide are currently under threat of drowning and destruction by sea-level rise, subsidence, and oceanic storms, highlighting the need to quantify their growth processes. Deltas are built through construction of sediment lobes, and emerging theories suggest that the size of delta lobes scales with backwater hydrodynamics, but these ideas are difficult to test on natural deltas that evolve slowly. We show results of the first laboratory delta built through successive deposition of lobes that maintain a constant size. We show that the characteristic size of delta lobes emerges because of a preferential avulsion node—the location where the river course periodically and abruptly shifts—that remains fixed spatially relative to the prograding shoreline. The preferential avulsion node in our experiments is a consequence of multiple river floods and Froude-subcritical flows that produce persistent nonuniform flows and a peak in net channel deposition within the backwater zone of the coastal river. In contrast, experimental deltas without multiple floods produce flows with uniform velocities and delta lobes that lack a characteristic size. Results have broad applications to sustainable management of deltas and for decoding their stratigraphic record on Earth and Mars

Epigenetic Changes with Dietary Soy in Cynomolgus Monkeys

Nutritional interventions are important alternatives for reducing the prevalence of many chronic diseases. Soy is a good source of protein that contains isoflavones, including genistein and daidzein, and may alter the risk of obesity, Type 2 diabetes, osteoporosis, cardiovascular disease, and reproductive cancers. We have shown previously in nonhuman primates that soy protein containing isoflavones leads to improved body weight, insulin sensitivity, lipid profiles, and atherosclerosis compared to protein without soy isoflavones (casein), and does not increase the risk of cancer. Since genistein has been shown to alter DNA methylation, we compared the methylation profiles of cynomolgus monkeys, from multiple tissues, eating two high-fat, typical American diets (TAD) with similar macronutrient contents, with or without soy protein. DNA methylation status was successfully determined for 80.6% of the probes in at least one tissue using Illumina's HumanMethylation27 BeadChip. Overall methylation increased in liver and muscle tissue when monkeys switched from the TAD-soy to the TAD-casein diets. Genes involved in epigenetic processes, specifically homeobox genes (HOXA5, HOXA11, and HOXB1), and ABCG5 were among those that changed between diets. These data support the use of the HumanMethylation27 BeadChip in cynomolgus monkeys and identify epigenetic changes associated with dietary interventions with soy protein that may potentially affect the etiology of complex diseases