RNA transcript profiling during zygotic gene activation in the preimplantation mouse embryo
RNA transcript profiling during zygotic gene activation in the preimplantation mouse embryo
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DOI：
10.1016/j.ydbio.2005.03.038
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发表时间：
2005-07-01
影响因子：
2.7
通讯作者：
Schultz, RM
中科院分区：
文献类型：
--
作者：
Zeng, FY;Schultz, RM
合子基因的激活对于植入前小鼠胚胎2-细胞期以后的发育是必不可少的。基于α-鹅膏蕈碱敏感的BrUTP掺入，转录起始于1-细胞胚胎，并且在2-细胞阶段期间显著观察到由新表达基因驱动的基因表达的主要重编程。叠加在基因组激活上的是在染色质结构水平上介导的转录抑制状态的发展。然而，在1-和2-细胞阶段表达的基因的身份描述得很差，因为那些参与介导转录抑制状态的基因。使用Affytek MOE 430小鼠基因芯片组，我们表征了在1-和2-细胞阶段期间表达的α-鹅膏蕈碱敏感基因组，并且我们使用表达分析系统探索器（EASE）和免疫途径分析（IPA）来鉴定由这些基因代表的生物和分子过程，以及它们之间的相互作用。我们发现，虽然1-细胞胚胎是转录活性的，但我们没有检测到MOE 430基因芯片上存在的任何转录本是α-鹅膏蕈碱敏感的。因此，BrUTP掺入所代表的意义仍然难以捉摸。在2-细胞胚胎中表达的基因中约有17%是α-鹅膏蕈碱敏感的。EASE分析表明，参与核糖体生物发生和组装，蛋白质合成，RNA代谢和转录的基因被过度代表，这表明在2-细胞阶段的基因组激活可能不像以前提出的那样是全球性的和混杂的。IPA暗示Myc和Hdac 1作为候选基因分别参与基因组激活和转录抑制状态的发展。(C)2005年爱思唯尔公司All rights reserved.
Zygotic gene activation is essential for development beyond the 2-cell stage in the preimplantation mouse embryo. Based on alpha-amanitin-sensitive BrUTP incorporation, transcription initiates in the 1-cell embryo and a major reprogramming of gene expression driven by newly expressed genes is prominently observed during the 2-cell stage. Superimposed on genome activation is the development of a transcriptionally repressive state that is mediated at the level of chromatin structure. The identity of the genes that are expressed during the 1- and 2-cell stages, however, is poorly described, as are those genes involved in mediating the transcriptionally repressive state. Using the Affymetrix MOE430 mouse GeneChip set, we characterized the set of (alpha-amanitin-sensitive genes expressed during the 1- and 2-cell stages, and we used Expression Analysis Systematic Explorer (EASE) and Ingenuity Pathway Analysis (IPA) to identify biological and molecular processes represented by these genes, as well as interactions among them. We find that although the 1-cell embryo is transcriptionally active, we did not detect any transcripts present on the MOE430 GeneChip set to be alpha-amanitin-sensitive. Thus, what the BrUTP incorporation represents remains elusive. About 17% of genes expressed in the 2-cell embryo are alpha-amanitin-sensitive. EASE analysis reveals that genes involved in ribosome biogenesis and assembly, protein synthesis, RNA metabolism and transcription are over-represented, suggesting that genome activation during 2-cell stage may not be as global and promiscuous as previously proposed. IPA implicated Myc and Hdac1 as candidate genes involved in genome activation and the development of the transcriptionally repressive state, respectively. (C) 2005 Elsevier Inc. All rights reserved.