Document Detail

Beta-globin regulation and long-range interactions.
MedLine Citation:
PMID:  18282504     Owner:  NLM     Status:  MEDLINE    
Transcriptional activation in higher eukaryotes frequently involves the long-range action of a number of regulatory DNA elements. One of the main questions in transcriptional regulation is how cis-regulatory elements communicate with the promoter of a gene over large distances. There has been a lively debate in recent years whether this communication takes place via a noncontact mechanism (linking, tracking) or via a contact mechanism (looping). The demonstration that the major regulatory element of the beta-globin locus, the locus control region (LCR), is in close proximity to the active beta-globin genes validates the contact model for long-range activation. Here, we will review the beta-globin locus as a model system to study long-range activation, briefly describe the different models for long-range activation, and summarize the recent findings that the LCR of the beta-globin locus is in close proximity to the active promoters. Although it is now firmly established that looping takes place within the beta-globin locus (and other loci), it is not clear how these long-range contacts are established and what the precise role is of the LCR. We will argue that the main action of the LCR takes place at the promoter and open reading frame of the gene itself and we will discuss key rate-limiting steps in transcriptional activation and the possible mechanisms by which they are influenced by the LCR.
Robert-Jan Palstra; Wouter de Laat; Frank Grosveld
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Advances in genetics     Volume:  61     ISSN:  0065-2660     ISO Abbreviation:  Adv. Genet.     Publication Date:  2008  
Date Detail:
Created Date:  2008-02-19     Completed Date:  2008-11-17     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  0370421     Medline TA:  Adv Genet     Country:  United States    
Other Details:
Languages:  eng     Pagination:  107-42     Citation Subset:  IM    
Department of Cell Biology and Genetics, Erasmus MC, 3000 CA Rotterdam, The Netherlands.
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MeSH Terms
Chromatin / chemistry,  physiology
Epistasis, Genetic*
Gene Expression Regulation / physiology*
Gene Order / physiology
Globins / genetics*
Locus Control Region / physiology
Models, Biological
Promoter Regions, Genetic / physiology
Transcription, Genetic / physiology
Reg. No./Substance:
0/Chromatin; 9004-22-2/Globins

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