共查询到20条相似文献,搜索用时 15 毫秒
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《Cellular signalling》2014,26(5):1075-1081
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E2F1 mediates DNA damage and apoptosis through HCF‐1 and the MLL family of histone methyltransferases 下载免费PDF全文
E2F1 is a key positive regulator of human cell proliferation and its activity is altered in essentially all human cancers. Deregulation of E2F1 leads to oncogenic DNA damage and anti‐oncogenic apoptosis. The molecular mechanisms by which E2F1 mediates these two processes are poorly understood but are important for understanding cancer progression. During the G1‐to‐S phase transition, E2F1 associates through a short DHQY sequence with the cell‐cycle regulator HCF‐1 together with the mixed‐lineage leukaemia (MLL) family of histone H3 lysine 4 (H3K4) methyltransferases. We show here that the DHQY HCF‐1‐binding sequence permits E2F1 to stimulate both DNA damage and apoptosis, and that HCF‐1 and the MLL family of H3K4 methyltransferases have important functions in these processes. Thus, HCF‐1 has a broader role in E2F1 function than appreciated earlier. Indeed, sequence changes in the E2F1 HCF‐1‐binding site can modulate both up and down the ability of E2F1 to induce apoptosis indicating that HCF‐1 association with E2F1 is a regulator of E2F1‐induced apoptosis. 相似文献
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目的:构建人E2F1基因原核表达质粒p GEX-KG-E2F1,并在大肠杆菌中诱导表达。随后验证纯化得到的E2F1蛋白可作为底物被甲基化转移酶修饰。方法:构建原核表达质粒p GEX-KG-E2F1,在大肠杆菌BL-21中经异丙基硫代半乳糖苷(IPTG)诱导表达,利用GST亲和层析法纯化表达的E2F1蛋白。随后将纯化的E2F1蛋白作为底物,组蛋白甲基化转移酶SET7/9作为酶进行体外同位素标记放射自显影实验,检测纯化的E2F1蛋白能否被甲基化。结果:酶切鉴定和测序结果证明成功构建了原核表达载体p GEX-KG-E2F1,SDS-PAGE检测结果证明实现了人E2F1基因在大肠杆菌中的可溶性表达,放射自显影证明纯化得到的E2F1蛋白可作为底物被甲基化转移酶SET7/9甲基化。结论:成功构建了转录因子E2F1体外甲基化体系,为筛选新的能甲基化E2F1的酶奠定基础。 相似文献
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Storre J Schäfer A Reichert N Barbero JL Hauser S Eilers M Gaubatz S 《The Journal of biological chemistry》2005,280(50):41380-41386
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We have used gene amplification in Drosophila follicle cells as a model of metazoan DNA replication to address whether changes in histone modifications are associated
with replication origin activation. We observe that replication initiation is associated with distinct histone modifications.
Acetylated lysines K5, K8, and K12 on histone H4 and K14 on histone H3 are specifically enriched during replication initiation
at the amplification origins. Strikingly, H4 acetylation persists at an amplification origin well after replication forks
have progressed significantly outward from the origin, indicating that H4 acetylation is associated with origin regulation
and not histone deposition at the replication forks. Origin recognition complex subunit 2 (orc2) mutants with severe amplification defects do not abolish H4 acetylation, whereas the dup/cdt1 mutant delays the appearance of acetylation foci, and mutants in rbf result in temporal persistence. These data indicate that core histone acetylation is associated with origin activity. Furthermore,
follicle cells undergoing gene amplification exhibit high levels of histone H1 phosphorylation. The patterns of H1 phosphorylation
provide insights into cell cycle states during amplification, as H1 kinase activity in follicle cells is responsive to high
Cyclin E activity, and it can be abolished by overexpressing the retinoblastoma homolog, Rbf, that represses Cyclin E. These
data suggest that amplification origins are able to initiate when the cells are in a late S-phase, when the genome is normally
not licensed for replication. 相似文献
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RBP1 recruits the mSIN3-histone deacetylase complex to the pocket of retinoblastoma tumor suppressor family proteins found in limited discrete regions of the nucleus at growth arrest 总被引:7,自引:0,他引:7 下载免费PDF全文
Lai A Kennedy BK Barbie DA Bertos NR Yang XJ Theberge MC Tsai SC Seto E Zhang Y Kuzmichev A Lane WS Reinberg D Harlow E Branton PE 《Molecular and cellular biology》2001,21(8):2918-2932
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《Cell cycle (Georgetown, Tex.)》2013,12(10):1942-1950
Histone modifications are associated with many fundamental biological processes in cells. An emerging notion from recent studies is that meiosis stage-dependent histone modifications are crucial for the oocyte development in mammals. In this paper, we review the changes and regulation as well as functions of histone modifications during meiotic maturation of mammalian oocyte, with particular emphasis on histone acetylation, phosphorylation and methylation. In general, dynamic and differential modification patterns have been revealed during oocyte maturation, indicative of functional requirement. Disruption of histone modifications leads to defective chromosome condensation and segregation, delayed maturation progression and even oocyte aging. Although several histone-modifying enzymes have been identified in mammalian oocytes, more works are necessary to determine how they direct histone modifications globally and individually in oocytes. Studies on chromatin modification during oocyte development will have implications for our understanding of the mechanisms controlling nuclear architecture and genomic stability in female germ line. 相似文献
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Marzio G Wagener C Gutierrez MI Cartwright P Helin K Giacca M 《The Journal of biological chemistry》2000,275(15):10887-10892