scholarly journals Long-range looping of a locus control region drives tissue-specific chromatin packing within a multigene cluster

2016 ◽  
Vol 44 (10) ◽  
pp. 4651-4664 ◽  
Author(s):  
Yu-Cheng Tsai ◽  
Nancy E. Cooke ◽  
Stephen A. Liebhaber
Keyword(s):  
Long Range ◽  
Control Region ◽  
Locus Control Region ◽  
Tissue Specific ◽  
Chromatin Packing

scholarly journals Locus Control Region Transcription Plays an Active Role in Long-Range Gene Activation

2006 ◽  
Vol 23 (4) ◽  
pp. 619
Author(s):  
Yugong Ho ◽  
Felice Elefant ◽  
Stephen A. Liebhaber ◽  
Nancy E. Cooke
Keyword(s):  
Long Range ◽  
Control Region ◽  
Gene Activation ◽  
Locus Control Region ◽  
Active Role

scholarly journals Requirement of an E1A-sensitive Coactivator for Long-range Transactivation by the β-Globin Locus Control Region

1999 ◽  
Vol 274 (38) ◽  
pp. 26850-26859 ◽  
Author(s):  
E. Camilla Forsberg ◽  
Kirby Johnson ◽  
Tatiana N. Zaboikina ◽  
Eric A. Mosser ◽  
Emery H. Bresnick
Keyword(s):  
Long Range ◽  
Control Region ◽  
Locus Control Region

New Concepts in Genome Regulation

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. SCI-47-SCI-47
Author(s):  
Ann Dean ◽  
Jongjoo Lee ◽  
Ryan Dale ◽  
Ivan Krivega
Keyword(s):  
Sickle Cell Disease ◽  
Long Range ◽  
Control Region ◽  
Sickle Cell ◽  
Globin Gene ◽  
Locus Control Region ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Cell Disease ◽  
Gamma Globin

Abstract Manipulating gene regulation to favor gamma-globin transcription over beta-globin transcription has been a goal of research in erythropoiesis for decades because of its relevance to amelioration of the pathophysiology of sickle cell disease and beta-thalassemia. A fundamental unanswered question in biology is how the unique pattern of gene expression, the transcriptome, of the many different individual mammalian cell types arises from the same genome blueprint and changes during development and differentiation. There is a growing appreciation that genome organization and the folding of chromosomes is a key determinant of gene transcription. Within this framework, enhancers function to increase the transcription of target genes over long linear distances. To accomplish this, enhancers engage in close physical contact with target promoters through chromosome folding, or looping. These long range interactions are orchestrated by cell type specific proteins and protein complexes that bind to enhancers and promoters and stabilize their interaction with each other. We have been studying LDB1, a member of an erythroid protein complex containing GATA1, TAL1 and LMO2. The LDB1complex activates erythroid genes through occupancy of virtually all erythroid enhancers. LDB1engages in homo- and heterotypic interactions with proteins occupying the promoters of erythroid genes to bring them into proximity with their enhancers. We find that enhancer long range looping activity can be redirected. Both targeting of the beta-globin locus control region to the gamma-globin gene in adult erythroid cells by the tethering of LDB1 or epigenetic unmasking of a silenced gamma-globin gene lead to increased locus control region (LCR)/gamma-globin contact frequency and reduced LCR/beta-globin contact. The outcome of these manipulations is robust, pan-cellular gamma-globin transcription activation with a concomitant reduction in beta-globin transcription. These examples suggest that chromosome looping can be considered a therapeutic target for gene activation or gene silencing to ameliorate genetic diseases such as sickle cell disease and beta-thalassemia. Disclosures No relevant conflicts of interest to declare.

scholarly journals Distinct Mechanisms Control RNA Polymerase II Recruitment to a Tissue-Specific Locus Control Region and a Downstream Promoter

2001 ◽  
Vol 8 (2) ◽  
pp. 465-471 ◽  
Author(s):  
Kirby D. Johnson ◽  
Heather M. Christensen ◽  
Bryan Zhao ◽  
Emery H. Bresnick
Keyword(s):  
Rna Polymerase ◽  
Rna Polymerase Ii ◽  
Control Region ◽  
Locus Control Region ◽  
Tissue Specific ◽  
Specific Locus

scholarly journals BRG1 requirement for long-range interaction of a locus control region with a downstream promoter

2009 ◽  
Vol 106 (7) ◽  
pp. 2259-2264 ◽  
Author(s):  
S.-I. Kim ◽  
S. J. Bultman ◽  
C. M. Kiefer ◽  
A. Dean ◽  
E. H. Bresnick
Keyword(s):  
Long Range ◽  
Control Region ◽  
Locus Control Region ◽  
Range Interaction ◽  
Long Range Interaction

scholarly journals A Defined Locus Control Region Determinant Links Chromatin Domain Acetylation with Long-Range Gene Activation

2002 ◽  
Vol 9 (2) ◽  
pp. 291-302 ◽  
Author(s):  
Yugong Ho ◽  
Felice Elefant ◽  
Nancy Cooke ◽  
Stephen Liebhaber
Keyword(s):  
Long Range ◽  
Control Region ◽  
Gene Activation ◽  
Locus Control Region ◽  
Chromatin Domain
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