The Drosophila MI-2 chromatin-remodeling factor regulates higher-order chromatin structure and cohesin dynamics in vivo.
The Drosophila MI-2 chromatin-remodeling factor regulates higher-order chromatin structure and cohesin dynamics in vivo.
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DOI：
10.1371/journal.pgen.1002878
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发表时间：
2012
期刊：
影响因子：
4.5
通讯作者：
Tamkun JW
中科院分区：
文献类型：
--
作者：
Fasulo B;Deuring R;Murawska M;Gause M;Dorighi KM;Schaaf CA;Dorsett D;Brehm A;Tamkun JW
dMi-2是一种高度保守的ATP依赖性染色质重塑因子，通过改变核小体的结构或定位来调节转录和细胞命运。在这里，我们报告了一个意想不到的作用dMi-2在果蝇的高阶染色质结构的调节。dMi-2功能的丧失导致唾液腺多线染色体失去其特征性带型，并且比正常情况下显得更加浓缩。相反，dMi-2的表达增加触发多线染色体的解凝聚，伴随着核体积的显著增加;这种作用相对较快，并且依赖于dMi-2的ATP酶活性。活体分析表明，dMi-2破坏了唾液腺多线染色体的排列染色单体之间的相互作用。dMi-2和粘着蛋白复合物在活性转录位点富集;光漂白后荧光恢复（FRAP）测定表明，dMi-2降低了粘着蛋白与多线染色体的稳定结合。这些发现表明，dMi-2是一个重要的调节染色体凝聚和凝聚素结合在间期细胞。DNA包装成染色质对于真核生物基因的组织和表达至关重要。核小体通过阻断转录因子和其他调节蛋白进入DNA来抑制转录。高于核小体水平的染色质组织水平，包括染色体折叠、配对和成环，也会对基因表达产生深远的影响。然而，高阶染色质结构的调节和用于控制基因表达的机制仍然知之甚少。使用果蝇作为模式生物，我们已经发现了一个意想不到的作用dMi-2，一个良好的特征ATP依赖性染色质重塑因子，在调节高阶染色质结构和内聚素在体内的动力学。dMi-2功能的抑制导致染色体凝聚，而dMi-2的表达升高触发多线和有丝分裂染色体的解凝聚，并且还使粘着蛋白结合不稳定。我们的研究结果表明，dMi-2可以调节转录和细胞分化在其他生物体，包括人类，通过改变高阶染色质结构或粘蛋白动力学。
dMi-2 is a highly conserved ATP-dependent chromatin-remodeling factor that regulates transcription and cell fates by altering the structure or positioning of nucleosomes. Here we report an unanticipated role for dMi-2 in the regulation of higher-order chromatin structure in Drosophila. Loss of dMi-2 function causes salivary gland polytene chromosomes to lose their characteristic banding pattern and appear more condensed than normal. Conversely, increased expression of dMi-2 triggers decondensation of polytene chromosomes accompanied by a significant increase in nuclear volume; this effect is relatively rapid and is dependent on the ATPase activity of dMi-2. Live analysis revealed that dMi-2 disrupts interactions between the aligned chromatids of salivary gland polytene chromosomes. dMi-2 and the cohesin complex are enriched at sites of active transcription; fluorescence-recovery after photobleaching (FRAP) assays showed that dMi-2 decreases stable association of cohesin with polytene chromosomes. These findings demonstrate that dMi-2 is an important regulator of both chromosome condensation and cohesin binding in interphase cells. The packaging of DNA into chromatin is critical for the organization and expression of eukaryotic genes. Nucleosomes repress transcription by blocking the access of transcription factors and other regulatory proteins to DNA. Levels of chromatin organization above the level of the nucleosome—including chromosome folding, pairing, and looping—can also have profound effects on gene expression. However, the mechanisms by which higher-order chromatin structure is regulated and used to control gene expression remain poorly understood. Using Drosophila as a model organism, we have discovered an unanticipated role for dMi-2, a well-characterized ATP-dependent chromatin- remodeling factor, in the regulation of higher-order chromatin structure and cohesin dynamics in vivo. The inhibition of dMi-2 function causes chromosomes to condense, while elevated expression of dMi-2 triggers the decondensation of polytene and mitotic chromosomes and also destabilizes cohesin binding. Our findings suggest that dMi-2 may regulate transcription and cellular differentiation in other organisms, including humans, by altering higher-order chromatin structure or cohesin dynamics.
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