GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis
GATA-1 transcription is controlled by distinct regulatory mechanisms during primitive and definitive erythropoiesis
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DOI：
10.1073/pnas.94.9.4487
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发表时间：
1997-04-29
影响因子：
11.1
通讯作者：
Yamamoto, M
中科院分区：
文献类型：
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作者：
Onodera, K;Takahashi, S;Yamamoto, M
转录因子GATA-1对于原始和最终红系细胞系的终末分化都是必需的，然而GATA-1本身的调节机制还不是很清楚。为了阐明GATA-1基因在体内是如何转录控制的，通过与报告基因融合来测试该基因的假定调节区，然后在转基因小鼠中进行检测。我们发现，位于红系第一外显子-3.9-2.6kb 5‘之间的转录调控元件作为激活元件，仅此序列就足以概括GATA-1的表达(但在原始红系细胞中是唯一的)，将GATA-1第一内含子的序列添加到这个上游元件中，为在原始和确定的红系细胞中完全重现GATA-1的表达提供了充分必要条件。第一内含子元件当连接到GATA-1基因启动子时并不具有内在的转录激活潜力，而需要上游激活元件才能激活其活性，这些实验表明GATA-1基因的表达在最终和原始红细胞生成过程中受离散的转录控制元件调节：5‘元件显示出原始红系细胞特异性激活元件所预期的性质，而GATA-1第一内含子内的新元件在最终红系细胞中特异性地增强这一活性。
Transcription factor GATA-1 is required for the terminal differentiation of both the primitive and definitive erythroid cell lineages, and yet the regulatory mechanisms of GATA-1 itself are not well understood. To clarify how the GATA-1 gene is transcriptionally controlled in vivo, presumptive regulatory regions of the gene were tested by fusion to a reporter gene and then examined in transgenic mice. We found that a transcriptional control element located between -3.9 and -2.6 kb 5' to the erythroid first exon serves as an activating element and that this sequence alone is sufficient to recapitulate the expression of GATA-1 (but uniquely in primitive erythroid cells), Addition of sequences from the GATA-1 first intron to this upstream element provides a necessary and sufficient condition for complete recapitulation of GATA-1 expression in both primitive and definitive erythroid cells. The first intron element does not possess intrinsic transcriptional activation potential when linked to the GATA-1 gene promoter but rather requires the upstream activating element for its activity, These experiments show that GATA-1 gene expression is regulated by discrete transcriptional control elements during definitive and primitive erythropoiesis: The 5' element displays properties anticipated for a primitive erythroid cell-specific activating element, and the novel element within the GATA-1 first intron specifically augments this activity in definitive erythroid cells.