The BCL11A network as a schematic target for various potential therapeutic modalities. BCL11A is shown occupying sequences within the β-globin cluster distal from the γ-globin genes themselves. It is subject to transcriptional activation by KLF1, which itself may be a target of c-Myb. BCL11A interacts with the NuRD nucleosome remodeling and deacetylase complex, which includes the ATPases CHD3/4 and histone deacetylases HDAC1/2 as well as MBD2. BCL11A also interacts with erythroid transcription factors including GATA1, FOG1, and SOX6. BCL11A could conceptually be therapeutically targeted by various strategies including: (1) decreasing its steady-state level, such as by preventing its activation by KLF1, or by RNA interference; (2) interfering with protein–protein interactions such as between BCL11A and GATA1; (3) interfering directly with BCL11A's protein–DNA interactions; (4) allosteric inhibitors of BCL11A itself or various partners; (5) active-site inhibitors of partner proteins with enzymatic activity such as HDAC1/2 and CHD3/4; (6) blocking associated chromatin reader modules, such as PHD fingers and chromodomains on CHD3/4 and MBD domain on MBD2; (7) direct genome editing, such as of critical BCL11A binding regulatory elements; and (8) as part of combination therapy with additional targets such as low-dose demethylase therapy.