Lamin B1 overexpression alters chromatin organization and gene expression.

Lamin B1 overexpression alters chromatin organization and gene expression.
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DOI:
10.1080/19491034.2023.2202548
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发表时间:
2023-12
期刊:
Nucleus (Austin, Tex.)
影响因子:
--
通讯作者:
Hetzer MW
Hetzer MW
中科院分区:
其他
文献类型:
--
作者:
Kaneshiro JM;Capitanio JS;Hetzer MW

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外周异染色质定位依赖于核膜相关蛋白和抑制性组蛋白修饰。在这里,我们表明,核纤层蛋白B1(LmnB1)的过度表达(OE)导致外周异染色质重新分配到异染色质灶内的核质。这些变化代表了通过独立于改变其他异染色质锚或组蛋白翻译后修饰的机制在核周边(NP)处异染色质结合的扰动。我们进一步表明,LmnB1 OE改变基因表达。这些变化不相关的H3K9me3的不同水平,但一个显着数量的失调基因可能是错误定位远离NP后LmnB1 OE。我们还观察到一个丰富的发展过程中上调的基因。这些基因中约74%在我们的细胞类型中通常被抑制,表明LmnB1 OE促进基因去抑制。这证明了LmnB1 OE对细胞命运的更广泛的影响,并强调了维持LmnB1适当水平的重要性。
Peripheral heterochromatin positioning depends on nuclear envelope associated proteins and repressive histone modifications. Here we show that overexpression (OE) of Lamin B1 (LmnB1) leads to the redistribution of peripheral heterochromatin into heterochromatic foci within the nucleoplasm. These changes represent a perturbation of heterochromatin binding at the nuclear periphery (NP) through a mechanism independent from altering other heterochromatin anchors or histone post-translational modifications. We further show that LmnB1 OE alters gene expression. These changes do not correlate with different levels of H3K9me3, but a significant number of the misregulated genes were likely mislocalized away from the NP upon LmnB1 OE. We also observed an enrichment of developmental processes amongst the upregulated genes. ~74% of these genes were normally repressed in our cell type, suggesting that LmnB1 OE promotes gene de-repression. This demonstrates a broader consequence of LmnB1 OE on cell fate, and highlights the importance of maintaining proper levels of LmnB1.
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