Stein Gary S, van Wijnen Andre J, Imbalzano Anthony N, Montecino Martin, Zaidi Sayyed K, Lian Jane B, Nickerson Jeffrey A, Stein Janet L
Department of Cell Biology, University of Massachusetts Medical School and Cancer Center, Worcester, MA 01655, USA.
Crit Rev Eukaryot Gene Expr. 2010;20(2):149-55. doi: 10.1615/critreveukargeneexpr.v20.i2.50.
The regulatory machinery that governs genetic and epigenetic control of gene expression for biological processes and cancer is organized in nuclear microenvironments. Strategic placement of transcription factors at target gene promoters in punctate microenvironments of interphase nuclei supports scaffolding of co- regulatory proteins and the convergence as well as integration of regulatory networks. The organization and localization of regulatory complexes within the nucleus can provide signatures that are linked to regulatory activity. Retention of transcription factors at gene loci in mitotic chromosomes contributes to epigenetic control of cell fate and lineage commitment, as well as to persistence of transformed and tumor phenotypes. Mechanistic understanding of the architectural assembly of regulatory machinery can serve as a basis for treating cancer with high specificity and minimal off-target effects.
调控生物过程和癌症中基因表达的遗传和表观遗传控制的调节机制，是在核微环境中组织起来的。转录因子在间期细胞核点状微环境中的靶基因启动子处的战略性定位，支持了共调节蛋白的支架作用以及调节网络的汇聚和整合。核内调节复合物的组织和定位可以提供与调节活性相关的特征。转录因子在有丝分裂染色体的基因位点上的保留，有助于细胞命运和谱系定型的表观遗传控制，以及转化和肿瘤表型的持续存在。对调节机制的结构组装的机理理解，可以作为高特异性和最小脱靶效应治疗癌症的基础。
