Wong Madeline M, Byun Jung S, Sacta Maria, Jin Qihuang, Baek SongJoon, Gardner Kevin
Genetics Branch, National Cancer Institute, Bethesda, Maryland, United States of America.
Laboratory of Endocrinology and Receptor Biology, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland, United States of America.
PLoS One. 2014 Jun 19;9(6):e99989. doi: 10.1371/journal.pone.0099989. eCollection 2014.
A central hallmark of epigenetic inheritance is the parental transmission of changes in patterns of gene expression to progeny without modification of DNA sequence. Although, the trans-generational conveyance of this molecular memory has been traditionally linked to covalent modification of histone and/or DNA, recent studies suggest a role for proteins that persist or remain bound within chromatin to "bookmark" specific loci for enhanced or potentiated responses in daughter cells immediately following cell division. In this report we describe a role for p300 in enabling gene bookmarking by pre-initiation complexes (PICs) containing RNA polymerase II (pol II), Mediator and TBP. Once formed these complexes require p300 to enable reacquisition of protein complex assemblies, chromatin modifications and long range chromatin interactions that facilitate post-mitotic transmission of transcriptional memory of prior environmental stimuli.
表观遗传的一个核心特征是基因表达模式的变化在不改变DNA序列的情况下由亲代传递给子代。虽然这种分子记忆的跨代传递传统上与组蛋白和/或DNA的共价修饰有关,但最近的研究表明,在染色质中持续存在或保持结合状态的蛋白质具有一种作用,即“标记”特定基因座,以便在细胞分裂后立即在子细胞中增强或强化反应。在本报告中,我们描述了p300在使含有RNA聚合酶II(pol II)、中介体和TBP的预起始复合物(PICs)进行基因标记方面的作用。一旦形成,这些复合物需要p300来重新获得蛋白质复合物组装、染色质修饰和长程染色质相互作用,从而促进对先前环境刺激的转录记忆的有丝分裂后传递。