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首页> 外文期刊>Nucleus >A demethylation deficient isoform of the lysine demethylase KDM2A interacts with pericentromeric heterochromatin in an HP1a-dependent manner
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A demethylation deficient isoform of the lysine demethylase KDM2A interacts with pericentromeric heterochromatin in an HP1a-dependent manner

机译：赖氨酸脱甲基酶KDM2A的去甲基化缺陷亚型以HP1a依赖性方式与着丝粒异染色质相互作用

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摘要

Histone modifications have a profound impact on the chromatin structure and gene expression and their correct establishment and recognition is essential for correct cell functioning. Malfunction of histone modifying proteins is associated with developmental defects and diseases and detailed characterization of these proteins is therefore very important. The lysine specific demethylase KDM2A is a CpG island binding protein that has been studied predominantly for its ability to regulate CpG island-associated gene promoters by demethylating their H3K36me2. However, very little attention has been paid to the alternative KDM2A isoform that lacks the N-terminal demethylation domain, KDM2A-SF. Here we characterized KDM2A-SF more in detail and we found that, unlike the canonical full length KDM2A-LF isoform, KDM2A-SF forms distinct nuclear heterochromatic bodies in an HP1a dependent manner. Our chromatin immunoprecipitation experiments further showed that KDM2A binds to transcriptionally silent pericentromeric regions that exhibit high levels of H3K36me2. H3K36me2 is the substrate of the KDM2A demethylation activity and the high levels of this histone modification in the KDM2A-bound pericentromeric regions imply that these regions are occupied by the demethylation deficient KDM2A-SF isoform.
机译：组蛋白修饰对染色质结构和基因表达具有深远的影响，其正确的建立和识别对于正确的细胞功能至关重要。组蛋白修饰蛋白的功能异常与发育缺陷和疾病有关，因此对这些蛋白进行详细表征非常重要。赖氨酸特异性脱甲基酶KDM2A是一种CpG岛结合蛋白，主要研究其通过使其H3K36me2脱甲基来调节与CpG岛相关的基因启动子的能力。但是，对缺乏N端去甲基化结构域KDM2A-SF的KDM2A异构体的关注却很少。在这里，我们更详细地描述了KDM2A-SF的特征，并且我们发现，与规范的全长KDM2A-LF亚型不同，KDM2A-SF以HP1a依赖的方式形成不同的核异色体。我们的染色质免疫沉淀实验进一步表明，KDM2A与表现出高水平H3K36me2的转录沉默周边着丝粒区域结合。 H3K36me2是KDM2A脱甲基活性的底物，在KDM2A结合的着丝粒区域中这种高组蛋白修饰的水平很高，这意味着这些区域被脱甲基缺陷的KDM2A-SF同工型占据。

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