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首页> 外文期刊>Molecular and Cellular Biology >Polycomb Group and SCF Ubiquitin Ligases Are Found in a Novel BCOR Complex That Is Recruited to BCL6 Targets
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Polycomb Group and SCF Ubiquitin Ligases Are Found in a Novel BCOR Complex That Is Recruited to BCL6 Targets

机译：在新型BCOR复合物中发现了Polycomb Group和SCF泛素中的利加斯物，该复合物被招募到BCL6目标

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摘要

The corepressor BCOR potentiates transcriptional repression by the proto-oncoprotein BCL6 and suppresses the transcriptional activity of a common mixed-lineage leukemia fusion partner, AF9. Mutations in human BCOR cause male lethal, X-linked oculofaciocardiodental syndrome. We identified a BCOR complex containing Polycomb group (PcG) and Skp-Cullin-F-box subcomplexes. The PcG proteins include RING1, RYBP, NSPC1, a Posterior Sex Combs homolog, and RNF2, an E3 ligase for the mono-ubiquitylation of H2A. BCOR complex components and mono-ubiquitylated H2A localize to BCL6 targets, indicating that the BCOR complex employs PcG proteins to expand the repertoire of enzymatic activities that can be recruited by BCL6. This also suggests that BCL6 can target PcG proteins to DNA. In addition, the BCOR complex contains components of a second ubiquitin E3 ligase, namely, SKP1 and FBXL10 (JHDM1B). We show that BCOR coimmunoprecipitates isoforms of FBXL10 which contain a JmjC domain that recently has been determined to have histone H3K36 demethylase activity. The recruitment of two distinct classes of E3 ubiquitin ligases and a histone demethylase by BCOR suggests that BCOR uses a unique combination of epigenetic modifications to direct gene silencing.
机译：核心抑制因子BCOR增强了原癌蛋白BCL6的转录抑制，并抑制了常见的混合谱系白血病融合伴侣AF9的转录活性。人BCOR的突变会导致男性致命的X连锁性眼动心电综合征。我们确定了包含聚梳基团（PcG）和Skp-Cullin-F-box亚复合物的BCOR复合物。 PcG蛋白包括RING1，RYBP，NSPC1，后性梳子同源物和RNF2（用于H2A单泛素化的E3连接酶）。 BCOR复合物成分和单泛素化的H2A定位于BCL6靶标，这表明BCOR复合物利用PcG蛋白来扩展BCL6可以募集的酶活性库。这也表明BCL6可以将PcG蛋白靶向DNA。此外，BCOR复合体还包含第二个泛素E3连接酶的成分，即SKP1和FBXL10（JHDM1B）。我们显示，BCOR coimmunoprecipitates FBXL10的亚型，其中包含一个JmjC域，最近已确定具有组蛋白H3K36脱甲基酶活性。 BCOR招募了两种不同类别的E3泛素连接酶和组蛋白脱甲基酶，这表明BCOR使用表观遗传修饰的独特组合来指导基因沉默。

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