HIC2

HIC2 (Hypermethylated in cancer 2) is a penta-dactyl zinc finger DNA binding protein containing a BTB/POZ domain that acts as a critical regulator of the fetal-to-adult hemoglobin switch. It functions by directly binding to and decommissioning the +55 erythroid enhancer of the BCL11A gene, thereby repressing BCL11A transcription. Since BCL11A is a major repressor of fetal hemoglobin (HbF), the downregulation of BCL11A by HIC2 leads to the induction of fetal γ-globin (HBG1/2) production. Research conducted at the Children's Hospital of Philadelphia and the University of Pennsylvania has demonstrated that HIC2 overexpression can significantly increase HbF levels and reduce cell sickling in sickle cell disease (SCD) patient-derived erythroid cells, suggesting its potential as a therapeutic target for SCD and β-thalassemia.

Other names

Hypermethylated in cancer 2ZBTB30ZBTB-30ZBTB 30Zinc finger and BTB domain-containing protein 30