Ludwig Institute for Cancer Research, La Jolla, California 92093, USA.
Genome Res. 2012 Aug;22(8):1426-36. doi: 10.1101/gr.124818.111. Epub 2012 Jun 8.
CBX5, CBX1, and CBX3 (HP1α, β, and γ, respectively) play an evolutionarily conserved role in the formation and maintenance of heterochromatin. In addition, CBX5, CBX1, and CBX3 may also participate in transcriptional regulation of genes. Recently, CBX3 binding to the bodies of a subset of genes has been observed in human and murine cells. However, the generality of this phenomenon and the role CBX3 may play in this context are unknown. Genome-wide localization analysis reveals CBX3 binding at genic regions, which strongly correlates with gene activity across multiple cell types. Depletion of CBX3 resulted in down-regulation of a subset of target genes. Loss of CBX3 binding leads to a more dramatic accumulation of unspliced nascent transcripts. In addition, we observed defective recruitment of splicing factors, including SNRNP70, to CBX3 target genes. Collectively, our data suggest a role for CBX3 in aiding in efficient cotranscriptional RNA processing.
CBX5、CBX1 和 CBX3(分别为 HP1α、β 和 γ)在异染色质的形成和维持中发挥着进化上保守的作用。此外,CBX5、CBX1 和 CBX3 也可能参与基因的转录调控。最近,在人类和鼠类细胞中观察到 CBX3 与一组基因的体结合。然而,这种现象的普遍性以及 CBX3 在这种情况下可能发挥的作用尚不清楚。全基因组定位分析显示 CBX3 结合在基因区域,这与多种细胞类型的基因活性强烈相关。CBX3 的耗竭导致一部分靶基因的下调。CBX3 结合的缺失导致未剪接的新生转录物更明显的积累。此外,我们观察到剪接因子(包括 SNRNP70)向 CBX3 靶基因的募集缺陷。总的来说,我们的数据表明 CBX3 在辅助有效的共转录 RNA 加工中发挥作用。