Department of Biochemistry and Molecular Biology, Oregon Health & Science University, Knight Cancer Institute, Portland, OR, USA.
Bioessays. 2012 Sep;34(9):760-70. doi: 10.1002/bies.201200035. Epub 2012 Jun 18.
Recent studies indicate that mammalian chromosomes contain discrete cis-acting loci that control replication timing, mitotic condensation, and stability of entire chromosomes. Disruption of the large non-coding RNA gene ASAR6 results in late replication, an under-condensed appearance during mitosis, and structural instability of human chromosome 6. Similarly, disruption of the mouse Xist gene in adult somatic cells results in a late replication and instability phenotype on the X chromosome. ASAR6 shares many characteristics with Xist, including random mono-allelic expression and asynchronous replication timing. Additional "chromosome engineering" studies indicate that certain chromosome rearrangements affecting many different chromosomes display this abnormal replication and instability phenotype. These observations suggest that all mammalian chromosomes contain "inactivation/stability centers" that control proper replication, condensation, and stability of individual chromosomes. Therefore, mammalian chromosomes contain four types of cis-acting elements, origins, telomeres, centromeres, and "inactivation/stability centers", all functioning to ensure proper replication, condensation, segregation, and stability of individual chromosomes.
最近的研究表明，哺乳动物染色体包含离散的顺式作用位点，这些位点控制复制时间、有丝分裂浓缩和整个染色体的稳定性。大型非编码 RNA 基因 ASAR6 的破坏导致复制时间延迟、有丝分裂期间的过度浓缩外观以及人类 6 号染色体的结构不稳定。同样，在成年体细胞中破坏小鼠 Xist 基因导致 X 染色体上的复制时间延迟和不稳定性表型。ASAR6 与 Xist 有许多共同特征，包括随机单等位基因表达和复制时间不同步。其他“染色体工程”研究表明，影响许多不同染色体的某些染色体重排表现出这种异常的复制和不稳定性表型。这些观察结果表明，所有哺乳动物染色体都包含“失活/稳定性中心”，这些中心控制单个染色体的正确复制、浓缩和稳定性。因此，哺乳动物染色体包含四种类型的顺式作用元件，即复制起点、端粒、着丝粒和“失活/稳定性中心”，它们都能确保单个染色体的正确复制、浓缩、分离和稳定性。
