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首页> 外文期刊>Nucleic Acids Research >The three-dimensional architecture of Hox cluster silencing
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The three-dimensional architecture of Hox cluster silencing

机译：Hox群集沉默的三维体系结构

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摘要

Spatial chromatin organization is emerging as an important mechanism to regulate the expression of genes. However, very little is known about genome architecture at high-resolution in vivo. Here, we mapped the three-dimensional organization of the human Hox clusters with chromosome conformation capture (3C) technology. We show that computational modeling of 3C data sets can identify candidate regulatory proteins of chromatin architecture and gene expression. Hox genes encode evolutionarily conserved master regulators of development which strict control has fascinated biologists for over 25 years. Proper transcriptional silencing is key to Hox function since premature expression can lead to developmental defects or human disease. We now show that the HoxA cluster is organized into multiple chromatin loops that are dependent on transcription activity. Long-range contacts were found in all four silent clusters but looping patterns were specific to each cluster. In contrast to the Drosophila homeotic bithorax complex (BX-C), we found that Polycomb proteins are only modestly required for human cluster looping and silencing. However, computational three-dimensional Hox cluster modeling identified the insulator-binding protein CTCF as a likely candidate mediating DNA loops in all clusters. Our data suggest that Hox cluster looping may represent an evolutionarily conserved structural mechanism of transcription regulation.
机译：空间染色质组织正在成为调节基因表达的重要机制。然而，关于高分辨率体内基因组结构的了解甚少。在这里，我们使用染色体构象捕获（3C）技术绘制了人类Hox簇的三维组织。我们表明，3C数据集的计算模型可以识别染色质结构和基因表达的候选调节蛋白。 Hox基因编码进化上保守的发育主要调控因子，严格控制已使生物学家着迷超过25年。适当的转录沉默是Hox功能的关键，因为过早表达会导致发育缺陷或人类疾病。现在，我们显示HoxA簇被组织成多个依赖于转录活性的染色质环。在所有四个静默群集中都发现了远程接触，但是循环模式特定于每个群集。与果蝇同源bithorax复合体（BX-C）相比，我们发现Polycomb蛋白仅是人类簇环和沉默所需的一部分。但是，计算三维Hox簇模型确定绝缘体结合蛋白CTCF是所有簇中介导DNA环的可能候选者。我们的数据表明，Hox簇环可能代表了转录调控的进化保守结构机制。

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