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Nucleic Acids Research Advance Access published online on August 17, 2007
Nucleic Acids Research, doi:10.1093/nar/gkm595
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© 2007 The Author(s)
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.0/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Molecular Biology

A facilitated tracking and transcription mechanism of long-range enhancer function

Xingguo Zhu, Jianhua Ling, Ling Zhang, Wenhu Pi, Min Wu and Dorothy Tuan*

Department of Biochemistry and Molecular Biology, School of Medicine, Medical College of Georgia, USA

*To whom correspondence should be addressed. Tel: 706 721 0272; Fax: 706 721 6608; Email: dtuanlo{at}mcg.edu

Received June 11, 2007. Revised July 9, 2007. Accepted July 18, 2007.

In the human {varepsilon}–globin gene locus, the HS2 enhancer in the Locus Control Region regulates transcription of the embryonic {varepsilon}-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 {varepsilon}-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.

The authors wish it to be known that, in their opinion, the first two authors should be regarded as joint First Authors.

Present address: Jianhua Ling, Department of Surgical Oncology, MD Anderson Cancer Center, Houston Texas 77030, USA


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