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首页> 外文期刊>Molecular and Cellular Biology >Identification of a Multifunctional Domain in Autonomously Replicating Sequence-Binding Factor 1 Required for Transcriptional Activation, DNA Replication, and Gene Silencing
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Identification of a Multifunctional Domain in Autonomously Replicating Sequence-Binding Factor 1 Required for Transcriptional Activation, DNA Replication, and Gene Silencing

机译:在转录激活,DNA复制和基因沉默所需的自主复制序列结合因子1中的多功能域的标识。

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Autonomously replicating sequence-binding factor 1 (ABF1) is a multifunctional, site-specific DNA binding protein that is essential for cell viability in Saccharomyces cerevisiae. ABF1 plays a direct role in transcriptional activation, stimulation of DNA replication, and gene silencing at the mating-type loci. Here we demonstrate that all three activities of ABF1 are conferred by the C terminus of the protein (amino acids [aa] 604 to 731). Furthermore, a detailed mutational analysis has revealed two important clusters of amino acid residues in the C terminus (C-terminal sequence 1 [CS1], aa 624 to 628; and CS2, aa 639 to 662). While both regions play a pivotal role in supporting cell viability, they make distinct contributions to ABF1 functions in various nuclear processes. CS1 specifically participates in transcriptional silencing and/or repression in a context-dependent manner, whereas CS2 is universally required for all three functions of ABF1. When tethered to specific regions of the genome, a 30-aa fragment that contains CS2 alone is sufficient for activation of transcription and chromosomal replication. In addition, CS2 is responsible for ABF1-mediated chromatin remodeling. Based on these results, we suggest that ABF1 may function as a chromatin-reorganizing factor to increase accessibility of the local chromatin structure, which in turn facilitates the action of additional factors to establish either an active or repressed chromatin state.
机译:自主复制序列结合因子1(ABF1)是一种多功能,特定位点的DNA结合蛋白,对于酿酒酵母(Saccharomyces cerevisiae)中的细胞生存力至关重要。 ABF1在转录激活,DNA复制刺激和交配型基因座基因沉默中起直接作用。在这里,我们证明了ABF1的所有三种活性都由蛋白质的C末端(氨基酸[aa] 604至731)赋予。此外,详细的突变分析显示,C末端有两个重要的氨基酸残基簇(C端序列1 [CS1],aa 624至628; CS2,aa 639至662)。虽然这两个区域在支持细胞活力中都起着关键作用,但它们对ABF1在各种核过程中的功能做出了独特的贡献。 CS1专门以上下文相关的方式参与转录沉默和/或抑制,而CS2是ABF1的所有三个功能的普遍要求。当拴系到基因组的特定区域时,仅包含CS2的30-aa片段足以激活转录和染色体复制。此外,CS2还负责ABF1介导的染色质重塑。根据这些结果,我们建议ABF1可能起着染色质重组因子的作用,以增加局部染色质结构的可及性,这反过来又促进了其他因子的作用,从而建立了活跃或受抑制的染色质状态。

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