期刊名称:Proceedings of the National Academy of Sciences
印刷版ISSN:0027-8424
电子版ISSN:1091-6490
出版年度:2002
卷号:99
期号:8
页码:5509-5514
DOI:10.1073/pnas.072084499
语种:English
出版社:The National Academy of Sciences of the United States of America
摘要:It is unclear whether the core promoter is involved in developmental regulation. To address this question, we mutated the TATA box of the human {gamma}-globin gene, produced transgenic mice, and examined the effect of the mutation during the course of mouse development. In our test system, the {gamma}-globin gene is expressed at similar levels in the embryonic and adult erythroid cells. The TATA box mutation dramatically reduced expression of the {gamma}-globin gene in the adult but not in embryonic erythroid cells. In addition, the disruption of the {gamma} TATA box significantly reduced the recruitment of TATA box-binding protein (TBP) in the adult cells, but not in embryonic cells, suggesting that the recruitment of TBP to the {gamma} gene promoter is developmentally specific. Similarly, the recruitment of transcription factor II B and RNA polymerase II to the {gamma} promoter was affected in the adult but not in embryonic cells. The distinct effects of the TATA mutation in the embryonic and adult developmental stages suggest that the basal transcription apparatus can be recruited to a core promoter in a developmental stage-dependent manner. The TATA mutation resulted in a shift of transcription initiation site 6 bp or longer upstream to the cap site both in the embryonic and adult erythrocytes. We conclude that the TATA box determines the initiation site but not the efficiency of transcription of the {gamma}-globin gene.