De Lucia Filomena, Ni Jian-Quan, Vaillant Catherine, Sun Fang-Lin
Friedrich Miescher Institute for Biomedical Research Maulbeerstrasse 66, CH-4058 Basel, Switzerland.
Nucleic Acids Res. 2005 May 19;33(9):2852-8. doi: 10.1093/nar/gki584. Print 2005.
Heterochromatin protein 1 (HP1) was originally described as a non-histone chromosomal protein and is required for transcriptional gene silencing and the formation of heterochromatin. Although it is localized primarily at pericentric heterochromatin, a scattered distribution over a large number of euchromatic loci is also evident. Here, we provide evidence that Drosophila HP1 is essential for the maintenance of active transcription of euchromatic genes functionally involved in cell-cycle progression, including those required for DNA replication and mitosis. Depletion of HP1 in proliferating embryonic cells caused aberrant progression of the cell cycle at S phase and G2/M phase, linked to aberrant chromosome segregation, cytokinesis, and an increase in apoptosis. The chromosomal distribution of Aurora B, and the level of phosphorylation of histone H3 serine 10 were also altered in the absence of HP1. Using chromatin immunoprecipitation analysis, we further demonstrate that the promoters of a number of cell-cycle regulator genes are bound to HP1, supporting a direct role for HP1 in their active transcription. Overall, our data suggest that HP1 is essential for the maintenance of cell-cycle progression and the transcription of cell-cycle regulatory genes. The results also support the view that HP1 is a positive regulator of transcription in euchromatin.
异染色质蛋白1(HP1)最初被描述为一种非组蛋白染色体蛋白,是转录基因沉默和异染色质形成所必需的。尽管它主要定位于着丝粒周围的异染色质,但在大量常染色质位点上的分散分布也很明显。在这里,我们提供证据表明,果蝇HP1对于维持功能上参与细胞周期进程的常染色质基因的活跃转录至关重要,包括那些DNA复制和有丝分裂所需的基因。增殖胚胎细胞中HP1的缺失导致细胞周期在S期和G2/M期出现异常进程,这与异常的染色体分离、胞质分裂以及细胞凋亡增加有关。在没有HP1的情况下,Aurora B的染色体分布以及组蛋白H3丝氨酸10的磷酸化水平也发生了改变。通过染色质免疫沉淀分析,我们进一步证明许多细胞周期调节基因的启动子与HP1结合,支持了HP1在其活跃转录中的直接作用。总体而言,我们的数据表明HP1对于维持细胞周期进程和细胞周期调节基因的转录至关重要。这些结果也支持了HP1是常染色质中转录的正调节因子这一观点。