Epigenetics and Chromatin Research Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
Nucleic Acids Res. 2012 Dec;40(22):11178-88. doi: 10.1093/nar/gks921. Epub 2012 Oct 11.
Recent evidence has shown that transcription is permissible through the purportedly repressive centromere domain, and that this transcriptional activity is of functional consequence. The best-studied example is transcription of the pericentric DNA repeats in the generation of siRNAs required for pericentric heterochromatin assembly in yeast. However, non-siRNA transcripts emanating from both pericentric and centromere core domains have also been detected in a cell cycle and cellular differentiation-dependent manner. Elevated levels of centromeric transcripts have also been detected in some cancers; however, it is still unclear how high levels of centromere transcripts may contribute towards disease progression. More recent studies have demonstrated that careful regulation of the histone modifications and transcription level at the centromere is vital for the recruitment of key centromere proteins and assembly of CENP-A domain. Here, we compare the transcriptional dynamics and function of various transcripts derived from pericentromeric and centromere core regions. We also propose a model in which the chromatin remodelling activity of transcription, and the resultant transcripts, contribute synergistically to perpetuate centromere chromatin identity.
最近的证据表明,转录是可以通过据称是抑制性着丝粒域进行的,并且这种转录活性具有功能后果。研究最充分的例子是在酵母中产生用于着丝粒异染色质组装的 siRNA 时,对着丝粒周围 DNA 重复序列的转录。然而,也已经以细胞周期和细胞分化依赖的方式检测到源自着丝粒核心域和着丝粒周围的非 siRNA 转录物。在一些癌症中也检测到较高水平的着丝粒转录物;然而,目前尚不清楚高浓度的着丝粒转录物如何促进疾病的发展。最近的研究表明,在着丝粒处精心调节组蛋白修饰和转录水平对于招募关键着丝粒蛋白和组装着丝粒蛋白 A 结构域至关重要。在这里,我们比较了源自着丝粒周围和着丝粒核心区域的各种转录本的转录动力学和功能。我们还提出了一个模型,其中转录的染色质重塑活性和由此产生的转录本协同作用,以维持着丝粒染色质的身份。