Manuelidis L, Borden J
Yale University School of Medicine, New Haven, CT 06510.
Chromosoma. 1988;96(6):397-410. doi: 10.1007/BF00303033.
Specific chromosome domains in interphase nuclei of neurons and glia were studied by three-dimensional (3-D) reconstruction of serial optical sections from in situ hybridized human CNS tissue. Overall patterns of centromere organization, delineated with alphoid repeats, were comparable to those seen in mouse, and are clearly conserved in mammalian evolution. Cloned probes from other individual chromosome domains were used to define interphase organization more precisely. Homologous chromosomes were spatially separated in nuclei. In large neurons, probes specific for 9q12, or 1q12 showed that at least one homolog was always compartmentalized together with centromeres on the nucleolus, while the second signal either abutted the nucleolus or was on the nuclear membrane. A telomeric Yq12 sequence also localized together with perinucleolar centromeres in a completely non-Rabl orientation. In astrocytes, these three chromosome regions were on the membrane and not necessarily associated with nucleoli. Therefore there are different patterns of interphase chromosome organization in functionally distinct cell types. In contrast to the above domains, a 1p36.3 telomeric sequence embedded in a large Alu-rich and early replicating chromosome region, was always found in an interior euchromatic nuclear compartment in both neurons and glial cells. In double hybridizations with 1q12 and 1p36.3 probes, 1p arms were clearly separated in all cells, and arms projected radially into the interior nucleoplasm with non-Rabl orientations. There was no absolute or rigid position for each 1p arm with respect to each other or to the major dendrite, indicating that individual chromosome arms may be dynamically positioned even in highly differentiated cell types. We suggest that centromeric and other highly repeated non-transcribed sequence domains may act as general organizing centers for cell type specific interphase patterns that are conserved in mammalian evolution. Such centers would allow selected groups of chromosome arms to extend into (and contract from) an interior, presumably transcriptionally active, nuclear compartment.
通过对原位杂交的人类中枢神经系统组织的连续光学切片进行三维（3-D）重建，研究了神经元和神经胶质细胞间期核中的特定染色体结构域。用α卫星重复序列描绘的着丝粒组织的总体模式与在小鼠中观察到的模式相似，并且在哺乳动物进化中明显保守。来自其他单个染色体结构域的克隆探针用于更精确地定义间期组织。同源染色体在核中在空间上是分开的。在大型神经元中，针对9q12或1q12的特异性探针显示，至少一个同源物总是与核仁上的着丝粒一起被分隔在一个区域，而第二个信号要么邻接核仁，要么位于核膜上。一个端粒Yq12序列也以完全非拉布尔方向与核仁周围的着丝粒定位在一起。在星形胶质细胞中，这三个染色体区域位于膜上，不一定与核仁相关。因此，在功能不同的细胞类型中存在不同的间期染色体组织模式。与上述结构域相反，一个嵌入富含Alu且早期复制的大染色体区域的1p36.3端粒序列，在神经元和神经胶质细胞中总是位于内部常染色质核区室中。在用1q12和1p36.3探针进行的双重杂交中，1p臂在所有细胞中明显分开，并且臂以非拉布尔方向径向伸入内部核质。每个1p臂相对于彼此或相对于主要树突没有绝对或固定的位置，这表明即使在高度分化的细胞类型中，单个染色体臂也可能动态定位。我们认为着丝粒和其他高度重复的非转录序列结构域可能作为细胞类型特异性间期模式的一般组织中心，这些模式在哺乳动物进化中是保守的。这样的中心将允许选定的染色体臂组延伸到（并从）一个内部的、可能是转录活跃区的核区室中（并收缩回来）。
