Quantitative signature for architectural organization of regulatory factors using intranuclear informatics
Quantitative signature for architectural organization of regulatory factors using intranuclear informatics
复制标题
DOI：
10.1242/jcs.01229
复制
发表时间：
2004-10
影响因子：
4
通讯作者：
Daniel W. Young;S. Zaidi;P. Furcinitti;A. Javed;A. V. van Wijnen;J. Stein;J. Lian;G. Stein
中科院分区：
文献类型：
--
作者：
Daniel W. Young;S. Zaidi;P. Furcinitti;A. Javed;A. V. van Wijnen;J. Stein;J. Lian;G. Stein
复制和基因表达的调节机制点状组织在超分子复合物中，这些超分子复合物在核微环境中划分。需要定量方法来了解核结构背景下调节机制的组装，并提供与生物控制的机制联系。我们开发了“核内信息学”来量化空间组织核域的功能相关参数。使用这种信息学策略，我们对子代细胞中 Runx (AML/Cbfa) 转录因子的局灶性亚核组织的有丝分裂后重建进行了表征。通过分析破坏 Runx 核内靶向保真度的点突变，我们建立了 Runx 结构域空间顺序的分子决定因素。我们的新方法提供了证据，表明 Runx 因子的结构组织可能对其组织特异性调节功能至关重要。
Regulatory machinery for replication and gene expression is punctately organized in supramolecular complexes that are compartmentalized in nuclear microenvironments. Quantitative approaches are required to understand the assembly of regulatory machinery within the context of nuclear architecture and to provide a mechanistic link with biological control. We have developed `intranuclear informatics' to quantify functionally relevant parameters of spatially organized nuclear domains. Using this informatics strategy we have characterized post-mitotic reestablishment of focal subnuclear organization of Runx (AML/Cbfa) transcription factors in progeny cells. By analyzing point mutations that abrogate fidelity of Runx intranuclear targeting, we establish molecular determinants for the spatial order of Runx domains. Our novel approach provides evidence that architectural organization of Runx factors may be fundamental to their tissue-specific regulatory function.