Developmental specificity of recruitment of TBP to the TATA box of the human gamma-globin gene.
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.
Duan
Zhi-Jun
ZJ
Division of Medical Genetics, Department of Medicine, University of Washington Medical School, Box 357720, Seattle, WA 98195, USA.
Fang
Xiangdong
X
Rohde
Alex
A
Han
Hemei
H
Stamatoyannopoulos
George
G
Li
Qiliang
Q
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus; D002843:Chromatin / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism*; D004912:Erythrocytes / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D016133:Polymerase Chain Reaction; D011233:Precipitin Tests; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D012333:RNA, Messenger / Q000378:metabolism; D016385:TATA Box / Q000235:genetics*; D035181:TATA-Box Binding Protein; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D014158:Transcription, Genetic
D002843:Chromatin; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D035181:TATA-Box Binding Protein; D014157:Transcription Factors; D005914:Globins