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使用新生 mRNA 作为转录活性指标鉴定早期 G1 期优先激活的基因。

Identification of preferentially reactivated genes during early G1 phase using nascent mRNA as an index of transcriptional activity.

机构信息

Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science, 2641 Yamazaki, Noda-shi, Chiba 278-8510, Japan.

出版信息

Biochem Biophys Res Commun. 2013 Jan 18;430(3):1005-10. doi: 10.1016/j.bbrc.2012.12.048. Epub 2012 Dec 19.

Abstract

During mammalian mitosis, transcription is silenced due to dissociation of transcription factors from DNA and chromosome condensation. At the end of mitosis, transcription is reactivated through chromosome relaxation and reloading of these factors to the DNA. Early G1 genes, which are preferentially reactivated during M/G1 transition, are important for maintenance of cellular function and are known to be strictly regulated. As only few early G1 genes have been identified to date, screening for early G1 genes by genome-wide analysis using nascent mRNA could contribute to the elucidation of the regulatory mechanisms during early G1. Here, we performed a detailed expression analysis for the M/G1 transition of mammalian cells by microarray analysis of nascent mRNA, and identified 298 early G1 genes. Analysis of these genes provides two important insights. Firstly, certain motifs are enriched in the upstream sequences of early G1 genes; from this we could predict candidate cognate transcription factors, including Sp1, which is recruited to the DNA in the early G1 phase. Secondly, we discovered that neighboring genes of early G1 genes were also frequently up-regulated in the G1 phase. Information about these numerous newly identified early G1 genes will likely contribute to an understanding of the regulatory mechanisms of the early G1 genes.

摘要

在哺乳动物有丝分裂过程中,转录因子与 DNA 解离和染色体浓缩导致转录沉默。有丝分裂末期,通过染色体松弛和这些因子重新加载到 DNA 上,转录被重新激活。早期 G1 基因在 M/G1 转换期间优先被重新激活,对维持细胞功能很重要,并且已知受到严格调控。由于迄今为止仅鉴定出少数早期 G1 基因,因此使用新生 mRNA 进行全基因组分析筛选早期 G1 基因可能有助于阐明早期 G1 期间的调控机制。在这里,我们通过新生 mRNA 的微阵列分析对哺乳动物细胞的 M/G1 转换进行了详细的表达分析,并鉴定出 298 个早期 G1 基因。对这些基因的分析提供了两个重要的见解。首先,某些基序在早期 G1 基因的上游序列中富集;由此,我们可以预测候选同源转录因子,包括在早期 G1 阶段被募集到 DNA 的 Sp1。其次,我们发现早期 G1 基因的邻近基因在 G1 期也经常被上调。这些新鉴定的大量早期 G1 基因的信息可能有助于理解早期 G1 基因的调控机制。

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