Controlling long-range genomic interactions at a native locus by targeted tethering of a looping factor.
Cell
; 149(6): 1233-44, 2012 Jun 08.
Article
de En
| MEDLINE
| ID: mdl-22682246
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 ß-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 ß-globin promoter in GATA1 null erythroblasts, in which the ß-globin locus is relaxed and inactive. Remarkably, targeting Ldb1 or only its self-association domain to the ß-globin promoter substantially activated ß-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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transcription génétique
/
Chromatine
/
Protéines de liaison à l'ADN
/
Globines bêta
/
Protéines à domaine LIM
Limites:
Animals
Langue:
En
Journal:
Cell
Année:
2012
Type de document:
Article
Pays d'affiliation:
États-Unis d'Amérique