Investigation of X chromosome organization before the onset of X-inactivation

描述（由申请人提供）：细胞核内亚结构和DNA序列的位置是高度组织化的，这种组织在调节染色质依赖性过程（如基因表达）中起作用。X染色体失活是一种实验上可行的现象，其中特定DNA序列位置的调节变化涉及基因表达的控制。在哺乳动物雌性细胞中，一条X染色体被沉默，以补偿雄性和雌性之间的X连锁基因的剂量，这一过程对雌性生存至关重要。在这里，我们建议调查的X染色体核组织，伴随X失活的调节变化的分子基础。所获得的见解可能更普遍适用，因为许多调节X失活的因素也调节其他环境中的基因表达。

DESCRIPTION (provided by applicant): The position of substructures and DNA sequences within the nucleus is highly organized, and this organization plays a role in regulating chromatin-dependent processes, such as gene expression. X chromosome inactivation is an experimentally amenable example of a phenomenon in which regulated changes in the location of specific DNA sequences is implicated in control of gene expression. In mammalian female cells, one X chromosome is silenced for dosage compensation of X-linked genes between males and females, and this process is essential for female survival. Here, we propose to investigate the molecular basis of the regulated changes in X chromosome nuclear organization that accompany X-inactivation. The insights gained are likely to be more generally applicable, since many of the factors that regulate X-inactivation also regulate gene expression in other contexts.