@article {liu_transcription_2021,
	title = {Transcription factor competition at the γ-globin promoters controls hemoglobin switching},
	journal = {Nature Genetics},
	year = {2021},
	note = {Publisher: Nature Publishing Group},
	pages = {1{\textendash}10},
	abstract = {BCL11A, the major regulator of fetal hemoglobin (HbF, α2γ2) level, represses γ-globin expression through direct promoter binding in adult erythroid cells in a switch to adult hemoglobin (HbA, α2β2). To uncover how BCL11A initiates repression, we used CRISPR{\textendash}Cas9, dCas9, dCas9-KRAB and dCas9-VP64 screens to dissect the γ-globin promoters and identified an activator element near the BCL11A-binding site. Using CUT\&RUN and base editing, we demonstrate that a proximal CCAAT box is occupied by the activator NF-Y. BCL11A competes with NF-Y binding through steric hindrance to initiate repression. Occupancy of NF-Y is rapidly established following BCL11A depletion, and precedes γ-globin derepression and locus control region (LCR){\textendash}globin loop formation. Our findings reveal that the switch from fetal to adult globin gene expression within the \textgreater50-kb β-globin gene cluster is initiated by competition between a stage-selective repressor and a ubiquitous activating factor within a remarkably discrete region of the γ-globin promoters.},
	issn = {1546-1718},
	doi = {10.1038/s41588-021-00798-y},
	url = {http://www.nature.com/articles/s41588-021-00798-y},
	author = {Liu, Nan and Xu, Shuqian and Yao, Qiuming and Zhu, Qian and Kai, Yan and Hsu, Jonathan Y. and Sakon, Phraew and Pinello, Luca and Yuan, Guo-Cheng and Bauer, Daniel E. and Orkin, Stuart H.}
}
