Transcription and replication result in distinct epigenetic marks following repression of early gene expression.
Transcription and replication result in distinct epigenetic marks following repression of early gene expression.
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DOI：
10.3389/fgene.2013.00140
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发表时间：
2013
影响因子：
3.7
通讯作者：
Milavetz B
中科院分区：
文献类型：
--
作者：
Kallestad L;Woods E;Christensen K;Gefroh A;Balakrishnan L;Milavetz B
猴病毒40(SV40)的早期转录产物T抗原与其同源调控序列--微染色体启动子I结合后，其早期转录受到抑制。因为SV40微小染色体经历复制和转录，所以在活跃的转录或DNA复制过程中可能会发生抑制。由于抑制经常通过引入特定形式的甲基化的组蛋白H3而在表观遗传学上被标记，我们表征了野生型SV40微染色体和突变型微染色体在转录和复制过程中H3尾部的甲基化，这些微染色体不抑制T抗原的表达。H3K9me1和H3K4me1清楚地标记了复制后抑制的微染色体，而早期转录抑制的微染色体则没有类似的标记。相反，对早期转录的抑制表现为H3K9me2水平的显着降低。当Aphidiclin抑制复制时，还观察到H3K9me1和H3K4me1复制依赖地引入到野生型SV40微染色体中。结果表明，与抑制相关的组蛋白修饰可能显著不同，这取决于被抑制的染色质是进行转录还是复制。
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.