Work

Regulation of the fetal hemoglobin silencing factor BCL11A

Year: 2016

Type: review

Abstract: The clinical severity of sickle cell disease and β-thalassemia, the major disorders of β-globin, can be ameliorated by increased production of fetal hemoglobin (HbF). Here, we provide a brief overview of the fetal-to-adult hemoglobin switch that occurs in humans shortly after birth and review our current understanding of one of the most potent known regulators of this switching process, the multiple zinc finger-containing transcription factor BCL11A. Originally identified in genome-wide association studies, multiple orthogonal lines of evidence have validated BCL11A as a key regulator of hemoglobin switching and as a promising therapeutic target for HbF induction. We discuss recent studies that have highlighted its importance in silencing the HbF-encoding genes and discuss opportunities that exist to further understand the regulation of BCL11A and its mechanism of action, which could provide new insight into opportunities to induce HbF for therapeutic purposes.

Source: Annals of the New York Academy of Sciences

DOI: 10.1111/nyas.13024

Authors: Anindita Basak, Vijay G. Sankaran

Institutions: Broad Institute, Boston Children's Hospital, Harvard University, Dana-Farber Cancer Institute, Manton Center for Orphan Disease Research

Language: English

Topic: Hemoglobinopathies and Related Disorders

Subfield: Genetics

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: National Institutes of Health, National Heart, Lung, and Blood Institute, National Institute of Diabetes and Digestive and Kidney Diseases