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首页> 外文期刊>Molecular and Cellular Biology >Formation of a Tissue-Specific Histone Acetylation Pattern by the Hematopoietic Transcription Factor GATA-1
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Formation of a Tissue-Specific Histone Acetylation Pattern by the Hematopoietic Transcription Factor GATA-1

机译：造血转录因子GATA-1形成组织特异性组蛋白乙酰化模式。

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One function of lineage-restricted transcription factors may be to control the formation of tissue-specific chromatin domains. In erythroid cells, the β-globin gene cluster undergoes developmentally regulated hyperacetylation of histones at the active globin genes and the locus control region (LCR). However, it is unknown which transcription factor(s) governs the establishment of this erythroid-specific chromatin domain. We measured histone acetylation at the β-globin locus in the erythroid cell line G1E, which is deficient for the essential hematopoietic transcription factor GATA-1. Restoration of GATA-1 activity in G1E cells led to a substantial increase in acetylation of histones H3 and H4 at the β-globin promoter and the LCR. Time course experiments showed that histone acetylation occurred rapidly after GATA-1 activation and coincided with globin gene expression, indicating that the effects of GATA-1 are direct. Moreover, increases in histone acetylation correlated with occupancy of GATA-1 and the acetyltransferase CBP at the locus in vivo. Together, these results suggest that GATA-1 and its cofactor CBP are essential for the formation of an erythroid-specific acetylation pattern that is permissive for high levels of gene expression.
机译：谱系限制性转录因子的一种功能可能是控制组织特异性染色质结构域的形成。在类红细胞中，β-珠蛋白基因簇在活性珠蛋白基因和基因座控制区（LCR）处经历了组蛋白的发育调控超乙酰化。但是，尚不清楚哪个转录因子控制该类红细胞特异性染色质结构域的建立。我们在红细胞系G1E的β-珠蛋白基因座上测量了组蛋白乙酰化，该蛋白缺乏必要的造血转录因子GATA-1。 G1E细胞中GATA-1活性的恢复导致β-珠蛋白启动子和LCR处组蛋白H3和H4的乙酰化显着增加。时程实验表明，组蛋白乙酰化在GATA-1激活后迅速发生，并与球蛋白基因表达相吻合，表明GATA-1的作用是直接的。此外，组蛋白乙酰化的增加与体内基因座中GATA-1和乙酰基转移酶CBP的占有率相关。总之，这些结果表明，GATA-1及其辅因子CBP对于形成类红细胞特异性乙酰化模式至关重要，该模式可允许高水平的基因表达。

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