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

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

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

In the human ε-globin gene locus, the HS2 enhancer in the Locus Control Region regulates transcription of the embryonic ε-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 ε-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.

Original languageEnglish (US)
Pages (from-to)5532-5544
Number of pages13
JournalNucleic Acids Research
Volume35
Issue number16
DOIs
StatePublished - Aug 2007

ASJC Scopus subject areas

  • Genetics

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