Lodhi Niraj, Kossenkov Andrew V, Tulin Alexei V
Fox Chase Cancer Center, Philadelphia, PA, 19111 USA.
The Wistar Institute, Philadelphia PA, 19104 USA.
Nucleic Acids Res. 2014 Jun;42(11):7028-38. doi: 10.1093/nar/gku415. Epub 2014 May 26.
Epigenetics are the heritable changes in gene expression or cellular phenotype caused by mechanisms other than changes in the underlying DNA sequence. After mitosis, it is thought that bookmarking transcription factors remain at promoters, regulating which genes become active and which remain silent. Herein, we demonstrate that poly(ADP-ribose)polymerase-1 (PARP-1) is a genome-wide epigenetic memory mark in mitotic chromatin, and we further show that the presence of PARP-1 is absolutely crucial for reactivation of transcription after mitosis. Based on these findings, a novel molecular model of epigenetic memory transmission through the cell cycle is proposed.
表观遗传学是指由潜在DNA序列变化以外的机制引起的基因表达或细胞表型的可遗传变化。有丝分裂后,人们认为书签式转录因子会保留在启动子处,调控哪些基因激活、哪些基因保持沉默。在此,我们证明聚(ADP-核糖)聚合酶-1(PARP-1)是有丝分裂染色质中全基因组范围的表观遗传记忆标记,并且我们进一步表明PARP-1的存在对于有丝分裂后转录的重新激活绝对至关重要。基于这些发现,我们提出了一种通过细胞周期进行表观遗传记忆传递的新型分子模型。