Enhancer-promoter pairs in the context of other interactions.

<p><i>Experimental Studies</i>, (<b>A</b>) Illustration of an enhancer (in yellow) spatially interacting with a promoter (blue) along a chromatin fiber. This coloring convention continues throughout the paper. (<b>B</b>) A recent study in Drosophila suggested a 7 kb chromatin loop formed between Su(Hw) insulators (orange) could decrease E-P interactions (red “X”) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Savitskaya1" target="_blank">[20]</a>. (<b>C</b>) Conversely, a 3 kb chromatin loop in the region between enhancer and promoter was proposed to increase E-P interactions. (<b>D</b>) Five arrangements for proposed looping interactions from three studies, left to right, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Kyrchanova1" target="_blank">[21]</a>, <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Kurukuti1" target="_blank">[22]</a>, and <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Comet1" target="_blank">[23]</a>. (<i>left</i>) a single Drosophila <i>gypsy</i> element between an enhancer and a promoter did not change their interactions (<i>top</i>), however an additional <i>gypsy</i> element upstream of the enhancer decreased E-P interactions (<i>bottom</i>) <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Kyrchanova1" target="_blank">[21]</a>. (<i>center</i>) at the mouse H19 locus, a regulatory element with multiple larger loops (55 kb and 25 kb) was suggested to control multiple E-P contacts; the enhancer can regulate the promoter before the loop, but cannot regulate the promoter within the loop <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Kurukuti1" target="_blank">[22]</a>. (<i>right</i>) chromatin loops may also modulate spatial interactions between silencing elements (e.g. PRE, black triangles) and their target promoters <a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#pcbi.1003867-Comet1" target="_blank">[23]</a>. The promoter within the loop is not silenced (<i>top</i>), whereas the promoter beyond the loop is silenced (<i>bottom</i>). <i>Polymer Simulations</i>, (<b>E</b>) Arrangement 1: polymer conformation where an enhancer is within a chromatin loop and a promoter is beyond the loop. (<b>F</b>) Arrangement 2: polymer conformation where an enhancer is before the loop and a promoter is after the loop. (<b>G</b>) (<i>left</i>) zoom-in on our polymer model of chromatin. The three large circles represent one monomer each; each monomer consists of three nucleosomes (small circles) or 500 bp. (<i>right</i>) full view of a sample polymer conformation showing a 30 kb chromatin loop (black) with highlighted loop-bases (orange) within a 1 Mb region.</p

Insulation and facilitation strength depends on enhancer-promoter positions.

<p>(<b>A</b>) Insulation (<i>left</i>) and facilitation (<i>right</i>) as a function of E-P genomic distance. For insulation, enhancer position remains fixed. For facilitation, an E-P pair is positioned symmetrically around the loop at each genomic distance. (<b>B</b>) Insulation for different positions of the enhancer within the loop with a constant genomic distance of 50 kb.</p

A chromatin loop alters the frequency of enhancer-promoter interactions.

<p>(<b>A</b>) Five sample conformations from polymer simulations with a 30 kb permanent loop (black) formed between two loop bases (orange) in a 1 Mb region of fiber. (<b>B</b>) Average heatmap (300 kb by 300 kb) for polymer simulations of the permanent, one-loop system, with a 30 kb loop (aggregated over 800,000 simulated conformations). Top and left edges show positions of the enhancer (yellow), promoter (blue), and loop bases (orange) for insulation and facilitation arrangements. (<b>C</b>) Schematics of E-P arrangements. (<i>top</i>) chromatin fiber without a fixed loop and with E-P genomic distance of 50 kb, as used to calculate expected (no-loop) contact frequencies (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#s4" target="_blank">Methods</a>). (<i>middle</i>) arrangement where insulation is observed, represented by the red “X”. (<i>bottom</i>) arrangement where facilitation is observed. (<b>D</b>) Contact frequency ratios (<a href="http://www.ploscompbiol.org/article/info:doi/10.1371/journal.pcbi.1003867#s4" target="_blank">Methods</a>) for insulation and facilitation arrangements with a 30 kb loop and 50 kb E-P genomic distance. Here and below, error bars indicate one standard deviation about the mean.</p

MOESM2 of Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

Additional file 2: Table S1. Transcription level of the genes from the studied region (CPM). Only genes with CPM > 1 in at least 2 replicates are presented. CPM values were averaged over replicates. Log2-fold change and FDR of difference between experiments are presented (see “Methods”). For genes that have not passed filtering procedure, only CPM are present

MOESM4 of Activation of the alpha-globin gene expression correlates with dramatic upregulation of nearby non-globin genes and changes in local and large-scale chromatin spatial structure

Additional file 4: Table S2. Sequences and characteristics of the 5C primers used in this study. 5C primers were designed using the alternating scheme in my5C.primers and chicken reference genome assembly galGal4

Additional file 1 of Lineage abundance estimation for SARS-CoV-2 in wastewater using transcriptome quantification techniques

Additional file 1. Includes all supplementary information, supplementary figures and supplementary tables

Additional file 2 of Lineage abundance estimation for SARS-CoV-2 in wastewater using transcriptome quantification techniques

Additional file 2. Review history