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Summary
Chromatin loops juxtapose distal enhancers with active promoters, but their molecular architecture and relationship with transcription remain unclear. In er
ythroid cells, the locus control region (LCR) and 尾-globin promoter form a chromatin loop that requires transcription factor GATA1 and the associated molecule Ldb1. We emplo
yed artificial zinc fingers (ZF) to tether Ldb1 to the 尾-globin promoter in GATA1 null er
ythroblasts, in which the 尾-globin locus is relaxed and inactive. Remarkabl
y, targeting Ldb1 or onl
y its self-association domain to the 尾-globin promoter substantiall
y activated 尾-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 phosphor
ylation of RNA pol
ymerase 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 causall
y underlies gene regulation.
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