Vertebrate HoxB gene expression requires DNA replication
Vertebrate HoxB gene expression requires DNA replication
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DOI：
10.1093/emboj/cdg352
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发表时间：
2003-07-15
期刊：
影响因子：
11.4
通讯作者：
Méchali, M
中科院分区：
文献类型：
--
作者：
Fisher, D;Méchali, M
为了研究体内DNA复制和转录的关系，我们研究了两个脊椎动物系统中HOX基因的激活：非洲爪哇胚胎发生和维甲酸诱导小鼠多能细胞P19分化。我们表明，非洲爪哇胚胎中期转变后的第一个细胞周期对于HoxB的激活是必要的和充分的，而正确的表达模式则需要较晚的细胞周期。在P19细胞中，HoxB的表达需要增殖，并且整个基因座在一个细胞周期内被激活。通过同步培养，我们发现HOXB基因的激活在一个细胞周期内是共线的，发生在S期，需要S期。在S期，HoxB基因复制较早，后期仍需复制才能达到最大表达。因此，HoxB基因的诱导是以依赖于DNA复制的方式进行的，并且只需要一个细胞周期。我们建议S阶段的重塑许可该基因座进行转录调控。
To study the relationship between DNA replication and transcription in vivo, we investigated Hox gene activation in two vertebrate systems: the embryogenesis of Xenopus and the retinoic acid-induced differentiation of pluripotent mouse P19 cells. We show that the first cell cycles following the mid- blastula transition in Xenopus are necessary and sufficient for HoxB activation, whereas later cell cycles are necessary for the correct expression pattern. In P19 cells, HoxB expression requires proliferation, and the entire locus is activated within one cell cycle. Using synchronous cultures, we found that activation of HoxB genes is colinear within a single cell cycle, occurs during S phase and requires S phase. The HoxB locus replicates early, whereas replication is still required for maximal expression later in S phase. Thus, induction of HoxB genes occurs in a DNA replication-dependent manner and requires only one cell cycle. We propose that S-phase remodelling licenses the locus for transcriptional regulation.