Authors' Affiliations: Vermont Cancer Center, College of Medicine; Department of Biochemistry, University of Vermont, Burlington, Vermont; Center for Biomedical Research; FONDAP Center for Genome Regulation, Universidad Andres Bello, Santiago, Chile; Departments of Orthopedic Surgery and Biochemistry and Molecular Biology, Mayo Clinic, Rochester, Minnesota.
Cancer Res. 2014 Jan 15;74(2):420-5. doi: 10.1158/0008-5472.CAN-13-2837. Epub 2014 Jan 9.
The regulatory information for phenotype, proliferation, and growth of normal and tumor cells must be maintained through genome replication in the S phase and cell division during mitosis. Epigenetic mechanisms that include DNA methylation, posttranslational modifications of histones, selective utilization of histone variants, and inheritable RNA molecules play pivotal roles in maintaining cellular identity through mitotic divisions. Recent studies demonstrate that mitotic occupancy of genes, which are determinants of cell fate, growth, and proliferation, by lineage-restricted transcription factors is a key epigenetic mechanism for retention and transmission of cellular expression memory. Evidence is emerging for the presence of distinct transcriptional regulatory microenvironments in mitotic chromosomes in which the genes bookmarked for reactivation postmitotically reside. Importantly, some oncoproteins are present in mitotic microenvironments where they occupy target genes during mitosis and may contribute to perpetuating the transformed phenotype. We discuss emerging regulatory implications of epigenetically bookmarking genes during mitosis for physiologic control as well as for the onset and progression of cancer.
维持正常和肿瘤细胞表型、增殖和生长的调控信息必须通过 S 期的基因组复制和有丝分裂期间的细胞分裂来实现。包括 DNA 甲基化、组蛋白的翻译后修饰、组蛋白变体的选择性利用以及可遗传的 RNA 分子在内的表观遗传机制,在有丝分裂分裂过程中对维持细胞身份起着关键作用。最近的研究表明,谱系限制转录因子对决定细胞命运、生长和增殖的基因在有丝分裂中的占据,是保留和传递细胞表达记忆的关键表观遗传机制。有证据表明,在有丝分裂染色体中存在着不同的转录调控微环境,其中标记为有丝分裂后重新激活的基因存在于这些微环境中。重要的是,一些癌蛋白存在于有丝分裂微环境中,它们在有丝分裂期间占据靶基因,并可能有助于维持转化表型。我们讨论了有丝分裂过程中表观遗传标记基因的新兴调控意义,这些意义既涉及生理控制,也涉及癌症的发生和进展。