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Transcription factor competition at the γ-globin promoters controls hemoglobin switching [ATACseq]

ABSTRACT: Transcription factor competition at the γ-globin promoters controls hemoglobin switching [ATACseq]

PROVIDER: PRJNA632565 | ENA |

REPOSITORIES: ENA

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Transcription factor competition at the γ-globin promoters controls hemoglobin switching [ATACseq]

Project description:BCL11A, the major regulator of HbF(α2γ2) level, represses γ-globin expression through direct promoter binding in adult erythroid cells in a switch to adult adult-type HbA (α2β2) production. Yet, the mechanism remains unclear. To uncover how BCL11A initiates repression, we used CRISPR/Cas9 and dCas9 screens to dissect the γ-globin promoters and identified an apparent activator element near the BCL11A binding region. Using CUT&RUN and base editing approaches, we demonstrate that this element, the proximal CCAAT box, is the binding site of transcription activator NF-Y. BCL11A competes with NF-Y binding through steric hindrance to initiate γ-globin repression, and the distance between the two motifs is critical for direct competition. Occupancy of NF-Y is rapidly established upon BCL11A depletion, and precedes γ-globin derepression and LCR-globin loop formation. Our findings reveal that the critical fetal-to-adult hemoglobin switch is initiated by the competition between transcription factors within a discrete region in the γ-globin promoters.

2020-12-22 | GSE150488 | GEO

Transcription factor competition at the γ-globin promoters controls hemoglobin switching

Project description:Transcription factor competition at the γ-globin promoters controls hemoglobin switching

| PRJNA632647 | ENA