MacCallum David E, Losada Ana, Kobayashi Ryuji, Hirano Tatsuya
Cold Spring Harbor Laboratory, Cold Spring Harbor, New York, NY 11724, USA.
Mol Biol Cell. 2002 Jan;13(1):25-39. doi: 10.1091/mbc.01-09-0441.
We previously characterized major components of mitotic chromosomes assembled in Xenopus laevis egg extracts and collectively referred to them as Xenopus chromosome-associated polypeptides (XCAPs). They included five subunits of the condensin complex essential for chromosome condensation. In an effort to identify novel proteins involved in this process, we have isolated XCAP-F and found it to be the Xenopus ortholog of ISWI, a chromatin remodeling ATPase. ISWI exists in two major complexes in Xenopus egg extracts. The first complex contains ACF1 and two low-molecular-weight subunits, most likely corresponding to Xenopus CHRAC. The second complex is a novel one that contains the Xenopus ortholog of the human Williams syndrome transcription factor (WSTF). In the absence of the ISWI complexes, the deposition of histones onto DNA is apparently normal, but the spacing of nucleosomes is greatly disturbed. Despite the poor spacing of nucleosomes, ISWI depletion has little effect on DNA replication, chromosome condensation or sister chromatid cohesion in the cell-free extracts. The association of ISWI with chromatin is cell cycle regulated and is under the control of the INCENP-aurora B kinase complex that phosphorylates histone H3 during mitosis. Apparently contradictory to the generally accepted model, we find that neither chromosome condensation nor chromosomal targeting of condensin is compromised when H3 phosphorylation is drastically reduced by depletion of INCENP-aurora B.
我们之前对非洲爪蟾卵提取物中组装的有丝分裂染色体的主要成分进行了表征,并将它们统称为非洲爪蟾染色体相关多肽(XCAPs)。它们包括染色体凝聚所必需的凝聚素复合物的五个亚基。为了鉴定参与这一过程的新蛋白质,我们分离出了XCAP-F,并发现它是染色质重塑ATP酶ISWI在非洲爪蟾中的同源物。ISWI在非洲爪蟾卵提取物中存在于两种主要复合物中。第一种复合物包含ACF1和两个低分子量亚基,很可能对应于非洲爪蟾的CHRAC。第二种复合物是一种新型复合物,包含人类威廉姆斯综合征转录因子(WSTF)在非洲爪蟾中的同源物。在没有ISWI复合物的情况下,组蛋白在DNA上的沉积显然正常,但核小体的间距受到极大干扰。尽管核小体间距不佳,但在无细胞提取物中,ISWI缺失对DNA复制、染色体凝聚或姐妹染色单体黏连几乎没有影响。ISWI与染色质的结合受细胞周期调控,并受有丝分裂期间使组蛋白H3磷酸化的INCENP-极光B激酶复合物的控制。与普遍接受的模型明显矛盾的是,我们发现当通过缺失INCENP-极光B使H3磷酸化大幅降低时,染色体凝聚和凝聚素的染色体靶向均未受损。