Department of Cell Biology and Department of Biology, Emory University, Atlanta, GA 30322, USA.
Nucleic Acids Res. 2012 Dec;40(22):11281-91. doi: 10.1093/nar/gks890. Epub 2012 Oct 9.
The regulatory mechanism of dosage compensation is the paramount example of epigenetic regulation at the chromosomal level. In Drosophila, this mechanism, designed to compensate for the difference in the dosage of X-linked genes between the sexes, depends on the MSL complex that enhances the transcription of the single dose of these genes in males. We have investigated the function of various subunits of the complex in mediating dosage compensation. Our results confirm that the highly enriched specific acetylation of histone H4 at lysine 16 of compensated genes by the histone acetyl transferase subunit MOF induces a more disorganized state of their chromatin. We have determined that the association of the MSL complex reduces the level of negative supercoiling of the deoxyribonucleic acid of compensated genes, and we have defined the role that the other subunits of the complex play in this topological modification. Lastly, we have analyzed the potential contribution of ISWI-containing remodeling complexes to the architecture of compensated chromatin, and we suggest a role for this remodeling factor in dosage compensation.
剂量补偿的调控机制是染色体水平上表观遗传调控的首要范例。在果蝇中，这种旨在补偿雌雄两性 X 连锁基因剂量差异的机制依赖于 MSL 复合物，该复合物可增强这些基因单剂量在雄性中的转录。我们研究了复合物的各种亚基在介导剂量补偿中的功能。我们的结果证实，由组蛋白乙酰转移酶亚基 MOF 介导的补偿基因组蛋白 H4 赖氨酸 16 的高度特异性乙酰化，诱导其染色质更为紊乱的状态。我们已经确定，MSL 复合物的结合降低了补偿基因脱氧核糖核酸的负超螺旋水平，并且我们定义了复合物的其他亚基在这种拓扑修饰中所起的作用。最后，我们分析了含有 ISWI 的重塑复合物对补偿染色质结构的潜在贡献，并提出了这种重塑因子在剂量补偿中的作用。
