A facilitated tracking and transcription mechanism of long-range enhancer function.
In the human epsilon-globin gene locus, the HS2 enhancer in the Locus Control Region regulates transcription of the embryonic epsilon-globin gene located over 10 kb away. The mechanism of long-range HS2 enhancer function was not fully established. Here we show that the HS2 enhancer complex containing the enhancer DNA together with RNA polymerase II (pol II) and TBP tracks along the intervening DNA, synthesizing short, polyadenylated, intergenic RNAs to ultimately loop with the epsilon-globin promoter. Guided by this facilitated tracking and transcription mechanism, the HS2 enhancer delivers pol II and TBP to the cis-linked globin promoter to activate mRNA synthesis from the target gene. An insulator inserted in the intervening DNA between the enhancer and the promoter traps the enhancer DNA and the associated pol II and TBP at the insulator site, blocking mid-stream the facilitated tracking and transcription mechanism of the enhancer complex, thereby blocking long-range enhancer function.
Zhu
Xingguo
X
Department of Biochemistry and Molecular Biology, School of Medicine, Medical College of Georgia, USA.
Ling
Jianhua
J
Zhang
Ling
L
Pi
Wenhu
W
Wu
Min
M
Tuan
Dorothy
D
D000818:Animals; D002645:Chickens / Q000235:genetics; D004742:Enhancer Elements, Genetic; D005914:Globins / Q000235:genetics*; D006801:Humans; D038101:Insulator Elements; D020014:K562 Cells; D019901:Locus Control Region; D008957:Models, Genetic; D009687:Nuclear Proteins / Q000378:metabolism; D000090243:Nucleophosmin; D026723:Polyadenylation; D011401:Promoter Regions, Genetic; D012319:RNA Polymerase II / Q000378:metabolism; D035181:TATA-Box Binding Protein / Q000378:metabolism; D014158:Transcription, Genetic; D015027:Zebrafish / Q000235:genetics
D009687:Nuclear Proteins; D035181:TATA-Box Binding Protein; D000090243:Nucleophosmin; D005914:Globins; D012319:RNA Polymerase II
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