Transcription arrest relief by S-II/TFIIS during gene expression in erythroblast differentiation
Transcription arrest relief by S-II/TFIIS during gene expression in erythroblast differentiation
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DOI：
10.1111/j.1365-2443.2008.01277.x
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发表时间：
2009-03-01
期刊：
影响因子：
2.1
通讯作者：
Sekimizu, Kazuhisa
中科院分区：
文献类型：
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作者：
Nagata, Makiko;Ito, Takahiro;Sekimizu, Kazuhisa
转录刺激因子S-II解除RNA聚合酶II（RNAPII）的转录延长停滞。缺乏S-II基因的小鼠（S-II KO小鼠）在妊娠中期死亡，成红细胞分化受损，Bcl-x基因表达降低。为了了解S-II在Bcl-x基因表达中的作用，我们研究了S-II KO小鼠Bcl-x基因上转录复合物的分布。在S-II KO小鼠中，Bcl-x基因内含子2处RNAPII的量减少，而转录起始因子TFIIB和RNAPII向启动子的募集没有减少。体外转录分析结果表明，Bcl-x基因内含子2存在一个转录阻滞位点，S-II能抑制Bcl-x基因内含子2的转录阻滞。此外，在S-II KO小鼠中，Bcl-x基因编码区的组蛋白乙酰化降低。在β（主要）-珠蛋白基因，其表达也减少了S-II KO小鼠，有RNAPII分布或组蛋白乙酰化没有变化，但组蛋白H3的量占据的编码区增加。这些结果表明，S-II参与转录的Bcl-x和β（主要）-珠蛋白基因在成红细胞分化，通过缓解转录停滞或影响组蛋白修饰的染色质模板。
Transcription stimulator S-II relieves RNA polymerase II (RNAPII) from transcription elongation arrest. Mice lacking the S-II gene (S-II KO mice) die at mid-gestation with impaired erythroblast differentiation, and have decreased expression of the Bcl-x gene. To understand a role of S-II in Bcl-x gene expression, we examined the distribution of transcription complex on the Bcl-x gene in S-II KO mice. The amount of RNAPII at intron 2 of the Bcl-x gene was decreased in S-II KO mice, whereas recruitment of transcription initiation factor TFIIB and RNAPII to the promoter was not decreased. Consistently, in vitro transcription analysis revealed the presence of a transcription arrest site in the Bcl-x gene intron 2, and transcription arrest at this site was overcome by S-II. Furthermore, histone acetylation on the coding region of the Bcl-x gene was decreased in S-II KO mice. In the beta(major)-globin gene, whose expression was also decreased in S-II KO mice, there were no changes in RNAPII distribution or histone acetylation, but the amount of histone H3 occupying the coding region was increased. These results suggest that S-II is involved in transcription of the Bcl-x and beta(major)-globin gene during erythroblast differentiation, by relieving transcription arrest or affecting histone modification on chromatin template.