Direct Promoter Repression by BCL11A Controls the Fetal to Adult Hemoglobin Switch.

ABSTRACT: Fetal hemoglobin (HbF, α₂γ₂) level is genetically controlled and modifies severity of adult hemoglobin (HbA, α₂β₂) disorders, sickle cell disease, and β-thalassemia. Common genetic variation affects expression of BCL11A, a regulator of HbF silencing. To uncover how BCL11A supports the developmental switch from γ- to β- globin, we use a functional assay and protein binding microarray to establish a requirement for a zinc-finger cluster in BCL11A in repression and identify a preferred DNA recognition sequence. This motif appears in embryonic and fetal-expressed globin promoters and is duplicated in γ-globin promoters. The more distal of the duplicated motifs is mutated in individuals with hereditary persistence of HbF. Using the CUT&RUN approach to

SUBMITTER: Liu N 

PROVIDER: S-EPMC5889339 | biostudies-literature | 2018 Apr

REPOSITORIES: biostudies-literature