Hu Xiao, Eszterhas Susan, Pallazzi Nicolas, Bouhassira Eric E, Fields Jennifer, Tanabe Osamu, Gerber Scott A, Bulger Michael, Engel James Douglas, Groudine Mark, Fiering Steven
Department of Microbiology/Immunology and Norris Cotton Cancer Center, Dartmouth Medical School, Hanover, NH 03756, USA.
Blood. 2007 Mar 1;109(5):2210-6. doi: 10.1182/blood-2006-06-029868. Epub 2006 Oct 31.
Mammalian beta-globin loci contain multiple genes that are activated at different developmental stages. Studies have suggested that the transcription of one gene in a locus can influence the expression of the other locus genes. The prevalent model to explain this transcriptional interference is that all potentially active genes compete for locus control region (LCR) activity. To investigate the influence of transcription by the murine embryonic genes on transcription of the other beta-like genes, we generated mice with deletions of the promoter regions of Ey and betah1 and measured transcription of the remaining genes. Deletion of the Ey and betah1 promoters increased transcription of betamajor and betaminor 2-fold to 3-fold during primitive erythropoiesis. Deletion of Ey did not affect betah1 nor did deletion of betah1 affect Ey, but Ey deletion uniquely activated transcription from betah0, a beta-like globin gene immediately downstream of Ey. Protein analysis showed that betah0 encodes a translatable beta-like globin protein that can pair with alpha globin. The lack of transcriptional interference between Ey and betah1 and the gene-specific repression of betah0 did not support LCR competition among the embryonic genes and suggested that direct transcriptional interference from Ey suppressed betah0.
哺乳动物的β-珠蛋白基因座包含多个在不同发育阶段被激活的基因。研究表明，一个基因座中的一个基因的转录可以影响该基因座中其他基因的表达。解释这种转录干扰的普遍模型是，所有潜在的活性基因都竞争基因座控制区（LCR）的活性。为了研究小鼠胚胎基因的转录对其他β样基因转录的影响，我们构建了缺失Ey和betah1启动子区域的小鼠，并测量了其余基因的转录情况。在原始红细胞生成过程中，Ey和betah1启动子的缺失使β-珠蛋白和β-珠蛋白的转录增加了2至3倍。Ey的缺失不影响betah1，betah1的缺失也不影响Ey，但Ey的缺失独特地激活了Ey下游紧邻的β样珠蛋白基因betah0的转录。蛋白质分析表明，betah0编码一种可翻译的β样珠蛋白，它可以与α珠蛋白配对。Ey和betah1之间缺乏转录干扰以及betah0的基因特异性抑制不支持胚胎基因之间的LCR竞争，并表明来自Ey的直接转录干扰抑制了betah0。
