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首页> 外文期刊>Molecular and Cellular Biology >In Vivo HP1 Targeting Causes Large-Scale Chromatin Condensation and Enhanced Histone Lysine Methylation
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In Vivo HP1 Targeting Causes Large-Scale Chromatin Condensation and Enhanced Histone Lysine Methylation

机译：体内HP1靶向导致大规模染色质凝结和增强组蛋白赖氨酸甲基化

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摘要

Changes in chromatin structure are a key aspect in the epigenetic regulation of gene expression. We have used a lac operator array system to visualize by light microscopy the effect of heterochromatin protein 1 (HP1) α (HP1α) and HP1β on large-scale chromatin structure in living mammalian cells. The structure of HP1, containing a chromodomain, a chromoshadow domain, and a hinge domain, allows it to bind to a variety of proteins. In vivo targeting of an enhanced green fluorescent protein-tagged HP1-lac repressor fusion to a lac operator-containing, gene-amplified chromosome region causes local condensation of the higher-order chromatin structure, recruitment of the histone methyltransferase SETDB1, and enhanced trimethylation of histone H3 lysine 9. Polycomb group proteins of both the HPC/HPH and the EED/EZH2 complexes, which are involved in the heritable repression of gene activity, are not recruited to the amplified chromosome region by HP1α and HP1β in vivo targeting. HP1α targeting causes the recruitment of endogenous HP1β to the chromatin region and vice versa, indicating a direct interaction between the two HP1 homologous proteins. Our findings indicate that HP1α and HP1β targeting is sufficient to induce heterochromatin formation.
机译：染色质结构的变化是基因表达的表观遗传调控的关键方面。我们已使用lac算子阵列系统通过光学显微镜可视化异染色质蛋白1（HP1）α（HP1α）和HP1β对哺乳动物活体细胞中大规模染色质结构的影响。 HP1的结构包含一个色域，一个色影域和一个铰链域，可使其与多种蛋白质结合。体内靶向增强型绿色荧光蛋白标签的HP1-lac阻遏物融合物至包含lac操纵子的基因扩增的染色体区域，引起高阶染色质结构的局部浓缩，组蛋白甲基转移酶SETDB1的募集和增强的三甲基化组蛋白H3赖氨酸9. HPC / HPH和EED / EZH2复合物的多梳基团蛋白均参与基因活性的遗传抑制，但HP1α和HP1β体内靶向并没有将其吸收到扩增的染色体区域。 HP1α靶向导致内源性HP1β募集到染色质区域，反之亦然，表明这两种HP1同源蛋白之间存在直接相互作用。我们的发现表明，HP1α和HP1β靶向足以诱导异染色质形成。

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