Department of Biochemistry and Molecular Biophysics, Columbia University, New York, NY, USA.
Department of Neuroscience, Columbia University, New York, NY, USA.
Nature. 2019 Jan;565(7740):448-453. doi: 10.1038/s41586-018-0845-0. Epub 2019 Jan 9.
The genome is partitioned into topologically associated domains and genomic compartments with shared chromatin valence. This architecture is constrained by the DNA polymer, which precludes interactions between genes on different chromosomes. Here we report a marked divergence from this pattern of nuclear organization that occurs in mouse olfactory sensory neurons. Chromatin conformation capture using in situ Hi-C on fluorescence-activated cell-sorted olfactory sensory neurons and their progenitors shows that olfactory receptor gene clusters from 18 chromosomes make specific and robust interchromosomal contacts that increase with differentiation of the cells. These contacts are orchestrated by intergenic olfactory receptor enhancers, the 'Greek islands', which first contribute to the formation of olfactory receptor compartments and then form a multi-chromosomal super-enhancer that associates with the single active olfactory receptor gene. The Greek-island-bound transcription factor LHX2 and adaptor protein LDB1 regulate the assembly and maintenance of olfactory receptor compartments, Greek island hubs and olfactory receptor transcription, providing mechanistic insights into and functional support for the role of trans interactions in gene expression.
基因组被分割成具有共享染色质价的拓扑相关结构域和基因组区室。这种结构受到 DNA 聚合酶的限制，从而阻止了不同染色体上基因之间的相互作用。在这里，我们报告了一种明显偏离这种核组织模式的现象，这种现象发生在小鼠嗅觉感觉神经元中。使用荧光激活细胞分选的嗅觉感觉神经元及其祖细胞的原位 Hi-C 进行染色质构象捕获表明，来自 18 条染色体的嗅觉受体基因簇会产生特定且强烈的染色体间接触，这种接触随着细胞的分化而增加。这些接触由基因间嗅觉受体增强子协调，即“希腊岛屿”，这些增强子首先有助于形成嗅觉受体区室，然后形成一个多染色体超级增强子，与单个活跃的嗅觉受体基因相关联。希腊岛结合转录因子 LHX2 和衔接蛋白 LDB1 调节嗅觉受体区室、希腊岛中心和嗅觉受体转录的组装和维持，为跨相互作用在基因表达中的作用提供了机制见解和功能支持。
