Controlling long range genomic interactions at a native locus by targeted tethering of a looping factor
By Wulan Deng, Jongjoo Lee, Hongxin Wang, Jeff Miller, A. Reik, P. Gregory, A. Dean, G. Blobel. Cell, 2012
733 citations recorded by the source corpus.
Summary 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 critical effector of GATA1-mediated loop formation and indicate that chromatin looping causally underlies gene regulation.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/cdb299afa8689f24e5b28428140f2fc291a60b6f
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In Molecular Biology
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Citations in the corpus
- Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data (2013, background): “Further, the looping interaction directly stimulates transcription by facilitating recruitment and phosphorylation of RNA polymerase II 39 .”
- CTCF Binding Polarity Determines Chromatin Looping. (2015, background): “Within TADs, chromatin loops can be formedbetween enhancers and distant target genes to increase their transcription (Deng et al., 2012).”
- YY1 Is a Structural Regulator of Enhancer-Promoter Loops (2017, unknown): “Nonetheless, most recent study of eukaryotic enhancer-promoter interactions has focused on cofactors that lack DNA binding capabilities and bridge enhancer-bound transcription factors and promoter-bound transcription apparatus (Allen and Taatjes, 2015; Deng et al., 2012; Jeronimo et al., 2016; Kagey”