A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse β-globin locus
A complex chromatin landscape revealed by patterns of nuclease sensitivity and histone modification within the mouse β-globin locus
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DOI：
10.1128/mcb.23.15.5234-5244.2003
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发表时间：
2003-08-01
影响因子：
5.3
通讯作者：
Groudine, M
中科院分区：
文献类型：
--
作者：
Bulger, M;Schübeler, D;Groudine, M
为了创建哺乳动物多基因座内染色质特征的扩展图谱，我们确定了成年红系组织中与小鼠β-珠蛋白基因相关的核酸酶敏感程度和组蛋白修饰模式。我们发现，核酸酶敏感区域包括β-珠蛋白基因和几个在红系细胞中不活跃的侧翼嗅觉受体基因。我们描述了在体内被转录因子CTCF结合的基因座两侧的增强子阻断或边界元件，但我们发现它们与基因座两侧核酸酶敏感性的转变或其内的组蛋白修饰模式不一致。此外，组蛋白H3K4的组蛋白超乙酰化和二甲基化并不是核酸酶敏感的小鼠β-珠蛋白结构域的统一特征，而是定义了该结构域中不同的亚域。我们的结果揭示了活跃的β-珠蛋白基因座的复杂染色质景观，并说明了伴随基因激活而产生的广泛结构变化的复杂性。
In order to create an extended map of chromatin features within a mammalian multigene locus, we have determined the extent of nuclease sensitivity and the pattern of histone modifications associated with the mouse beta-globin genes in adult erythroid tissue. We show that the nuclease-sensitive domain encompasses the beta-globin genes along with several flanking olfactory receptor genes that are inactive in erythroid cells. We describe enhancer-blocking or boundary elements on either side of the locus that are bound in vivo by the transcription factor CTCF, but we found that they do not coincide with transitions in nuclease sensitivity flanking the locus or with patterns of histone modifications within it. In addition, histone hyperacetylation and dimethylation of histone H3 K4 are not uniform features of the nuclease-sensitive mouse beta-globin domain but rather define distinct subdomains within it. Our results reveal a complex chromatin landscape for the active beta-globin locus and illustrate the complexity of broad structural changes that accompany gene activation.