Bozhenok Ludmila, Wade Paul A, Varga-Weisz Patrick
Marie Curie Research Institute, Oxted, Surrey RH8 0TL, UK.
EMBO J. 2002 May 1;21(9):2231-41. doi: 10.1093/emboj/21.9.2231.
The Williams Syndrome Transcription Factor (WSTF), the product of the WBSCR9 gene, is invariably deleted in the haploinsufficiency Williams-Beuren Syndrome. Along with the nucleosome-dependent ATPase ISWI, WSTF forms a novel chromatin remodeling complex, WICH (WSTF-ISWI chromatin remodeling complex), which is conserved in vertebrates. The WICH complex was purified to homogeneity from Xenopus egg extract and was found to contain only WSTF and ISWI. In mouse cells, WSTF interacts with the SNF2H isoform of ISWI. WSTF accumulates in pericentric heterochromatin coincident with the replication of these structures, suggesting a role for WSTF in the replication of heterochromatin. Such a role is supported by the in vitro activity of both the mouse and frog WICH complexes: they are involved in the assembly of regular spaced nucleosomal arrays. In contrast to the related ISWI-interacting protein ACF1/WCRF180, WSTF binds stably to mitotic chromosomes. As dysfunction of other chromatin remodeling factors often has severe effects on development, haploinsufficiency of WSTF may explain some of the phenotypes associated with this disease.
威廉姆斯综合征转录因子（WSTF）是WBSCR9基因的产物，在单倍剂量不足的威廉姆斯-博伦综合征中总是缺失。WSTF与依赖核小体的ATP酶ISWI一起，形成了一种新型染色质重塑复合体WICH（WSTF-ISWI染色质重塑复合体），该复合体在脊椎动物中保守。WICH复合体从非洲爪蟾卵提取物中纯化至同质，发现仅包含WSTF和ISWI。在小鼠细胞中，WSTF与ISWI的SNF2H亚型相互作用。WSTF在着丝粒周围异染色质中积累，与这些结构的复制同时发生，提示WSTF在异染色质复制中起作用。小鼠和青蛙的WICH复合体的体外活性支持了这一作用：它们参与规则间隔核小体阵列的组装。与相关的与ISWI相互作用的蛋白ACF1/WCRF180不同，WSTF稳定地结合有丝分裂染色体。由于其他染色质重塑因子的功能障碍通常对发育有严重影响，WSTF的单倍剂量不足可能解释了与该疾病相关的一些表型。
