LDB1-mediated enhancer looping can be established independent of mediator and cohesin

Nucleic Acids Research
Ivan Krivega, Ann Dean

Abstract

Mechanistic studies in erythroid cells indicate that LDB1, as part of a GATA1/TAL1/LMO2 complex, brings erythroid-expressed genes into proximity with enhancers for transcription activation. The role of co-activators in establishing this long-range interaction is poorly understood. Here we tested the contributions of the RNA Pol II pre-initiation complex (PIC), mediator and cohesin to establishment of locus control region (LCR)/β-globin proximity. CRISPR/Cas9 editing of the β-globin promoter to eliminate the RNA Pol II PIC by deleting the TATA-box resulted in loss of transcription, but enhancer-promoter interaction was unaffected. Additional deletion of the promoter GATA1 site eliminated LDB1 complex and mediator occupancy and resulted in loss of LCR/β-globin proximity. To separate the roles of LDB1 and mediator in LCR looping, we expressed a looping-competent but transcription-activation deficient form of LDB1 in LDB1 knock down cells: LCR/β-globin proximity was restored without mediator core occupancy. Further, Cas9-directed tethering of mutant LDB1 to the β-globin promoter forced LCR loop formation in the absence of mediator or cohesin occupancy. Moreover, ENCODE data and our chromatin immunoprecipitation results indicate tha...Continue Reading

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Citations

Dec 3, 2017·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Cia-Hin Lau, Yousin Suh
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Jul 11, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Jin KangAeRi Kim

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Datasets Mentioned

BETA
GM12878

Methods Mentioned

BETA
transgenic
transfection
immunoprecipitation
ChIP
conformation capture assay
capture-Hi-C
RNA-seq
ChIP-seq
Co-immunoprecipitation
co-IP

Software Mentioned

MACS2
BEDTtools
jaccard
R
BEDTools
BEDTools multinter
ChromHMM
MEME
Bowtie2
MS Excel

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