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Another surprising fact is that genes that control zinc levels within cells are known to be associated with cardiovascular diseases including hypertension, and hypertension is also a known side effect of zinc deficiency. This new research provides explanations for these previously known associations.

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High blood pressure, or hypertension, is the leading modifiable risk factor for cardiovascular diseases and premature death worldwide. And key to treating patients with conditions ranging from chest pain to stroke is understanding the intricacies of how the cells around arteries and other blood vessels work to control blood pressure. While the importance of metals like potassium and calcium in this process are known, a new discovery about a critical and underappreciated role of another metal—zinc—offers a potential new pathway for therapies to treat hypertension.

The study results were published recently in Nature Communications.

All the body’s functions depend on arteries channeling oxygen-rich blood —energy—to where it’s needed, and smooth muscle cells within these vessels direct how fast or slow the blood gets to each destination. As smooth muscles contract, they narrow the artery and increase the blood pressure, and as the muscle relaxes, the artery expands and blood pressure falls. If the blood pressure is too low the blood flow will not be enough to sustain a person’s body with oxygen and nutrients. If the blood pressure is too high, the blood vessels risk being damaged or even ruptured.

While carrying out high-throughput chromosome conformation capture (Hi-C) analysis on stage 8 (s8) X. tropicalis embryos, we noticed that chromatin interactions plotted at 100-kilobase (kb) resolution using the reference genome v.9.1 showed inversions, misplacements and gaps in nearly every chromosome (Fig. 1a and Extended Data Fig. 1). Thus, to accurately characterize the genome folding patterns in X. tropicalis, we conducted a de novo genome assembly of X. tropicalis using Hi-C and single-molecule sequencing^42,43,44 (Fig. 1b). The newly assembled genome fixed most misplacements, inversions and gaps (Fig. 1c, d, Extended Data Fig. 2 and Supplementary Fig. 1). This new version of the genome was also longer (Supplementary Table 1 and Fig. 1e) and centromere interactions can now be detected (Supplementary Fig. 2). During the preparation of this work, v.10.0 of the X. tropicalis genome was released. While both v.10.0 and our assembly fixed major errors, both versions are still flawed with visually identifiable errors (Supplementary Fig. 1; blue and green arrows). A comparison of the three versions is shown in Supplementary Table 1. Conclusions from the following analyses are the same whether we used v.10.0 or our assembled genome.

To examine when the 3D chromatin architecture is established in X. tropicalis, we generated in situ Hi-C maps on hand-picked s8 embryos (Fig. 2a). A high-resolution (5-kb) inspection of chromatin contact heatmaps failed to reveal any distinct patterns (Fig. 2b), indicating the lack of structural organization before MBT. Next, we determined whether chromatin structures will emerge when rapid synchronized cell division ends by carrying out in situ Hi-C on s9 embryos. Although weak, TAD-like structures appeared across chromatin contact heatmaps (Fig. 2b), suggesting that TAD structures start forming as MBT begins in X. tropicalis.

We continued to examine the changes in chromatin conformation at later developmental stages (stages 10, 11, 12, 13, 15, 17, and 23) after major ZGA (Fig. 2b). TAD boundaries increased progressively from 2471 at s9 to 3000 at s11 (Extended Data Fig. 3a, b). This level was maintained throughout the later developmental stages and with relatively stable median TAD sizes (Extended Data Fig. 3a, b). Consistent with this pattern, the percentage of the genome folded into TADs positively correlated with the number of TADs established at each stage (Extended Data Fig. 3c). Overall, TAD borders were stable during development (Fig. 2c) and contained a high level of gene expression (Extended Data Fig. 3D, e).