Delattre Marion, Spierer Anne, Jaquet Yannis, Spierer Pierre
Department of Zoology and Animal Biology, University of Geneva, 30, quai Ernest-Ansermet, 1211, Geneva 4, Switzerland.
J Cell Sci. 2004 Dec 1;117(Pt 25):6239-47. doi: 10.1242/jcs.01549.
The Su(var)3-7 protein is essential for fly viability, and several lines of evidence support its key importance in heterochromatin formation: it binds to pericentric heterochromatin, it potently suppresses variegation and it interacts with HP1. However, the mode of action of Su(var)3-7 is poorly understood. Here we investigate in vivo the consequences of increased Su(var)3-7 expression on fly viability and chromatin structure. A large excess of Su(var)3-7 induces lethality, whereas lower doses permit survival and cause spectacular changes in the morphology of polytene chromosomes in males, and to a lesser extent in females. The male X is always the most affected chromosome: it becomes highly condensed and shortened, and its characteristic banding pattern is modified. In addition, Su(var)3-7 was found over the complete length of all chromosomes. This event coincides with the appearance of heterochromatin markers such as histone H3K9 dimethylation and HP1 at many sites on autosomes and, more strikingly, on the male X chromosome. These two features are strictly dependent on the histone-methyltransferase Su(var)3-9, whereas the generalised localisation of Su(var)3-7 is not. These data provide evidence for a dose-dependent regulatory role of Su(var)3-7 in chromosome morphology and heterochromatin formation. Moreover they show that Su(var)3-7 expression is sufficient to induce Su(var)3-9-dependent ectopic heterochromatinisation and suggest a functional link between Su(var)3-7 and the histone-methyltransferase Su(var)3-9.
Su(var)3-7蛋白对果蝇的生存能力至关重要，多条证据支持其在异染色质形成中的关键重要性：它与着丝粒周围异染色质结合，能有效抑制花斑现象，且与HP1相互作用。然而，Su(var)3-7的作用模式尚不清楚。在此，我们在体内研究了Su(var)3-7表达增加对果蝇生存能力和染色质结构的影响。大量过量的Su(var)3-7会导致致死性，而较低剂量则允许存活，并导致雄性果蝇多线染色体形态发生显著变化，雌性果蝇的变化程度较小。雄性X染色体始终是受影响最严重的染色体：它变得高度浓缩和缩短，其特征性的带型也发生改变。此外，在所有染色体的全长上都发现了Su(var)3-7。这一事件与异染色质标记物的出现同时发生，如组蛋白H3K9二甲基化和HP1在常染色体的许多位点出现，更显著的是在雄性X染色体上。这两个特征严格依赖于组蛋白甲基转移酶Su(var)3-9，而Su(var)3-7的普遍定位则不然。这些数据为Su(var)3-7在染色体形态和异染色质形成中的剂量依赖性调节作用提供了证据。此外，它们表明Su(var)3-7的表达足以诱导依赖于Su(var)3-9的异位异染色质化，并暗示了Su(var)3-7与组蛋白甲基转移酶Su(var)3-9之间的功能联系。
