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High-resolution mapping of heterochromatin redistribution in a Drosophila position-effect variegation model

机译:果蝇位置效应斑驳模型中异染色质重新分布的高分辨率映射

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Background Position-effect variegation (PEV) is the stochastic transcriptional silencing of a gene positioned adjacent to heterochromatin. white-mottled X-chromosomal inversions in Drosophila are classic PEV models that show variegation of the eye color gene white due to its relocation next to pericentric heterochromatin. It has been suggested that in these models the spreading of heterochromatin across the rearrangement breakpoint causes the silencing of white. However, the extent of this spreading and the precise pattern of heterochromatin redistribution have remained unclear. To obtain insight into the mechanism of PEV, we constructed high-resolution binding maps of Heterochromatin Protein 1 (HP1) on white-mottled chromosomes. Results We find that HP1 invades euchromatin across the inversion breakpoints over ~175 kb and ~30 kb, causing de novo association of HP1 with 20 genes. However, HP1 binding levels in these regions show substantial local variation, and white is the most strongly bound gene. Remarkably, white is also the only gene that is detectably repressed by heterochromatin. Furthermore, we find that HP1 binding to the invaded region is particularly sensitive to the dosage of the histone methyltransferase Su(var)3-9, indicating that the de novo formed heterochromatin is less stable than naturally occurring constitutive heterochromatin. Conclusion Our molecular maps demonstrate that heterochromatin can invade a normally euchromatic region, yet the strength of HP1 binding and effects on gene expression are highly dependent on local context. Our data suggest that the white gene has an unusual intrinsic affinity for heterochromatin, which may cause this gene to be more sensitive to PEV than most other genes.
机译:背景位置效应变异(PEV)是与异染色质相邻的基因的随机转录沉默。果蝇中呈白色斑驳的X染色体倒置是经典的PEV模型,由于眼睛颜色基因白色紧挨着外周中心异染色质而重新定位,因此显示出多样化的眼睛颜色基因。已经提出,在这些模型中,异染色质在重排断裂点上的扩散导致白色的沉默。然而,这种扩散的程度和异染色质重新分布的精确模式仍不清楚。为了深入了解PEV的机制,我们在斑驳的染色体上构建了异染色质蛋白1(HP1)的高分辨率结合图。结果我们发现,HP1跨大约175 kb和〜30 kb的转折点侵入了常染色质,从而导致HP1与20个基因从头建立了联系。但是,这些区域中的HP1结合水平显示出明显的局部差异,而白色是结合最强的基因。值得注意的是,白色也是唯一被异染色质抑制的基因。此外,我们发现与入侵区域结合的HP1对组蛋白甲基转移酶Su(var)3-9的剂量特别敏感,这表明从头形成的异染色质不如天然组成型异染色质稳定。结论我们的分子图谱表明异染色质可以侵入正常的常色区,但是HP1结合的强度以及对基因表达的影响高度依赖于局部环境。我们的数据表明,白色基因对异染色质具有不同寻常的内在亲和力,这可能导致该基因比大多数其他基因对PEV更敏感。

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