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Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor.
- Source :
-
Cell [Cell] 2012 Jun 08; Vol. 149 (6), pp. 1233-44. - Publication Year :
- 2012
-
Abstract
- Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In erythroid cells, the locus control region (LCR) and β-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We employed artificial zinc fingers (ZF) to tether Ldb1 to the β-globin promoter in GATA1 null erythroblasts, in which the β-globin locus is relaxed and inactive. Remarkably, targeting Ldb1 or only its self-association domain to the β-globin promoter substantially activated β-globin transcription in the absence of GATA1. Promoter-tethered Ldb1 interacted with endogenous Ldb1 complexes at the LCR to form a chromatin loop, causing recruitment and phosphorylation of RNA polymerase II. ZF-Ldb1 proteins were inactive at alleles lacking the LCR, demonstrating that their activities depend on long-range interactions. Our findings establish Ldb1 as a critical effector of GATA1-mediated loop formation and indicate that chromatin looping causally underlies gene regulation.<br /> (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Subjects :
- Animals
Cell Line
Cell Separation
DNA-Binding Proteins chemistry
Embryo, Mammalian cytology
Erythroblasts metabolism
Female
GATA1 Transcription Factor metabolism
Gene Expression Regulation
LIM Domain Proteins chemistry
Male
Mice
Promoter Regions, Genetic
Protein Structure, Tertiary
Zinc Fingers
Chromatin metabolism
DNA-Binding Proteins metabolism
LIM Domain Proteins metabolism
Transcription, Genetic
beta-Globins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-4172
- Volume :
- 149
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Cell
- Publication Type :
- Academic Journal
- Accession number :
- 22682246
- Full Text :
- https://doi.org/10.1016/j.cell.2012.03.051