Chromosome structure in mammals is thought to regulate transcription by modulating three-dimensional interactions between enhancers and promoters, notably through CTCF-mediated loops and topologically associating domains (TADs)1–4. However, how chromosome interactions are actually translated into transcriptional outputs remains unclear. Here, to address this question, we use an assay to position an enhancer at large numbers of densely spaced chromosomal locations relative to a fixed promoter, and measure promoter output and interactions within a genomic region with minimal regulatory and structural complexity. A quantitative analysis of hundreds of cell lines reveals that the transcriptional effect of an enhancer depends on its contact probabilities with the promoter through a nonlinear relationship. Mathematical modelling suggests that nonlinearity might arise from transient enhancer–promoter interactions being translated into slower promoter bursting dynamics in individual cells, therefore uncoupling the temporal dynamics of interactions from those of transcription. This uncovers a potential mechanism of how distal enhancers act from large genomic distances, and of how topologically associating domain boundaries block distal enhancers. Finally, we show that enhancer strength also determines absolute transcription levels as well as the sensitivity of a promoter to CTCF-mediated transcriptional insulation. Our measurements establish general principles for the context-dependent role of chromosome structure in long-range transcriptional regulation.
Mounting concern about NO3 pollution of the nation's ground and surface waters make accurate N‐fertilizer recommendations increasingly important. A study was initiated in 1984 to determine if presidedress soil or corn stalk (Zea mays L.) NO3 concentrations could be used to predict soil N availability and the need for sidedress N fertilizer. Nitrate concentration was determined in the surface 30 cm of soil and in the lower 10 cm of corn stalks 22 to 37 d after emergence (corn was in the 5‐ to 6‐leaf stage). Eighty‐seven N‐response experiments were conducted over a 4‐yr period in central and southern Pennsylvania. A number of these sites were on fields that had received high rates of manure in the past. Corn stalk NO3 concentration was not an accurate predictor of soil N availability nor of the probability that a site would respond to N fertilizer. The NO3 concentration in the surface 30 cm of soil 4 to 5 wk after emergence was a good indicator of whether a response to sidedress N fertilizer would be attained. The best critical level for separating responsive from nonresponsive sites was 21 mg NO3‐N kg−1. No sites responded to N fertilizer when the soil NO3‐N concentration was greater than 25 mg kg−1. Soil NO3 concentration and soil N‐supplying capability (NSC) at soil NO3 levels below the critical level were not correlated well enough (r2 = 0.34) to use the predicted NSC for adjusting N‐fertilizer recommendations. As a result, the best use of this test in Pennsylvania appears to be in identification of nonresponsive sites rather than predicting N‐fertilizer rates. Use of this test by farmers in Pennsylvania will help minimize the practice of applying “insurance” N when N contributions from manure and legumes in rotations are uncertain.
Cellular stress leads to reprogramming of mRNA translation and formation of stress granules (SGs), membraneless organelles consisting of mRNA and RNA-binding proteins. Although the function of SGs remains largely unknown, it is widely assumed they contain exclusively nontranslating mRNA. Here we re-examine this hypothesis using single-molecule imaging of mRNA translation in living cells. While our data confirms that non-translating mRNAs are preferentially recruited to SGs, we find unequivocal evidence for translation of mRNA localized to SGs. Our data indicate that SG-associated translation is not rare and that the entire translation cycle (initiation, elongation and termination) can occur for these transcripts. Furthermore, translating mRNAs can be observed transitioning between the cytosol and SGs without changing their translational status. Together, these results argue against a direct role for SGs in inhibition of mRNA translation.
Highlights d A minority of mRNAs localize to stress granules (SGs) and P-bodies (PBs) d Very few mRNAs move directly from SGs into PBs d LARP1 anchors 5 0 TOP transcripts within SGs and PBs d Granule localization in stress does not affect translation or decay during recovery
In this paper, the native and nonnative floras of Boston, New York, Philadelphia, Washington, D.C., Detroit, Chicago, Minneapolis, and St. Louis urban areas are compared, and overall native diversity and nonnative diversity are correlated with a variety of factors. A total of 4,159 species has been reported in the eight urban areas. Of these, 2,708 (65.1%) are native to one or more of the urban areas and 1,451 (34.9%) are nonnative. Only 316 (11.6%) of the native species and only 109 (7.5%) of the nonnative species are common to all of the urban areas. When the similarity of native species is compared, Boston, New York, Philadelphia, and Washington, D.C., form a cluster, as do Detroit, Chicago, and Minneapolis; St. Louis is least similar to the other seven urban areas. Correlating climatic variables (growing season, temperature) and geographical variables (area, latitude, longitude) with species richness showed that nonnative species richness was most strongly correlated with longitude (probably as a function of age of settlement). This is in contrast * Published Online June 24, 2003 with past research on native species showing a strong correlation of native species richness with latitude and elevations due to climatic differences present at different latitudes and elevations. Further studies that incorporate data from additional urban areas are needed to determine if nonnative species richness continues to be strongly correlated with time of a city's settlement.
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