National Research Centre Frontiers in Genetics, School of Life Sciences, Ecole Polytechnique Fédérale (EPFL), Lausanne, Switzerland.
Science. 2011 Oct 14;334(6053):222-5. doi: 10.1126/science.1207194.
The spatial and temporal control of Hox gene transcription is essential for patterning the vertebrate body axis. Although this process involves changes in histone posttranslational modifications, the existence of particular three-dimensional (3D) architectures remained to be assessed in vivo. Using high-resolution chromatin conformation capture methodology, we examined the spatial configuration of Hox clusters in embryonic mouse tissues where different Hox genes are active. When the cluster is transcriptionally inactive, Hox genes associate into a single 3D structure delimited from flanking regions. Once transcription starts, Hox clusters switch to a bimodal 3D organization where newly activated genes progressively cluster into a transcriptionally active compartment. This transition in spatial configurations coincides with the dynamics of chromatin marks, which label the progression of the gene clusters from a negative to a positive transcription status. This spatial compartmentalization may be key to process the colinear activation of these compact gene clusters.
Hox 基因转录的时空调控对于脊椎动物体轴的模式形成至关重要。尽管这一过程涉及组蛋白翻译后修饰的变化，但特定的三维（3D）结构的存在仍有待在体内进行评估。我们使用高分辨率染色质构象捕获方法，研究了不同 Hox 基因在胚胎小鼠组织中活跃时 Hox 簇的空间构象。当簇处于转录失活状态时，Hox 基因缔合成一个从侧翼区域限定的单一 3D 结构。一旦转录开始，Hox 簇就会切换到双峰 3D 组织形式，新激活的基因逐渐聚集到转录活跃的隔室中。这种空间构象的转变与染色质标记的动态一致，这些标记标志着基因簇从负转录状态向正转录状态的进展。这种空间分区可能是处理这些紧凑基因簇共线性激活的关键。
