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转录和复制导致早期基因表达受到抑制后出现不同的表观遗传标记。

Transcription and replication result in distinct epigenetic marks following repression of early gene expression.

机构信息

Department of Biochemistry and Molecular Biology, University of North Dakota School of Medicine and Health Sciences Grand Forks, ND, USA.

出版信息

Front Genet. 2013 Jul 30;4:140. doi: 10.3389/fgene.2013.00140. eCollection 2013.

DOI:10.3389/fgene.2013.00140
PMID:23914205
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3728471/
Abstract

Simian virus 40 (SV40) early transcription is repressed when the product of early transcription, T-antigen, binds to its cognate regulatory sequence, Site I, in the promoter of the SV40 minichromosome. Because SV40 minichromosomes undergo replication and transcription potentially repression could occur during active transcription or during DNA replication. Since repression is frequently epigenetically marked by the introduction of specific forms of methylated histone H3, we characterized the methylation of H3 tails during transcription and replication in wild-type SV40 minichromosomes and mutant minichromosomes which did not repress T-antigen expression. While repressed minichromosomes following replication were clearly marked with H3K9me1 and H3K4me1, minichromosomes repressed during early transcription were not similarly marked. Instead repression of early transcription was marked by a significant reduction in the level of H3K9me2. The replication dependent introduction of H3K9me1 and H3K4me1 into wild-type SV40 minichromosomes was also observed when replication was inhibited with aphidicolin. The results indicate that the histone modifications associated with repression can differ significantly depending upon whether the chromatin being repressed is undergoing transcription or replication.

摘要

猿猴病毒 40(SV40)早期转录受到抑制,当早期转录产物 T 抗原结合到其在 SV40 微染色体启动子中的同源调节序列 Site I 时。因为 SV40 微染色体可能进行复制和转录,所以潜在的抑制作用可能发生在活跃的转录过程中或在 DNA 复制过程中。由于抑制作用通常通过引入特定形式的甲基化组蛋白 H3 来进行表观遗传标记,因此我们在野生型 SV40 微染色体和不抑制 T 抗原表达的突变微染色体中转录和复制过程中对 H3 尾巴的甲基化进行了表征。虽然复制后的受抑制微染色体明显标记有 H3K9me1 和 H3K4me1,但在早期转录过程中受到抑制的微染色体并没有被同样标记。相反,早期转录的抑制作用通过 H3K9me2 水平的显著降低来标记。当用阿霉素抑制复制时,也观察到复制依赖性 H3K9me1 和 H3K4me1 向野生型 SV40 微染色体中的引入。结果表明,与抑制相关的组蛋白修饰可能因正在被抑制的染色质是否正在进行转录或复制而有很大差异。

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