GSE97671
KLF1 directly activates expression of the novel fetal globin repressor, ZBTB7A/LRF, in erythroid cells
Genes encoding the human ß-like hemoglobin proteins undergo a developmental switch from fetal ?-globin to adult ß-globin expression at around the time of birth. ß-hemoglobinopathies, such  as  sickle  cell  disease  and  ß-thalassemia, result  from  mutations affecting  the  adult  ß-globin gene.  The  only  treatment  options  currently available  carry  significant  side-effects. Analyses of heritable variations in fetal hemoglobin (HbF) levels have provided evidence that reactivation of the silenced fetal ?-globin genes in adult erythroid cells is a promising therapy. The ?-globin repressor BCL11A has become the major focus with several studies investigating its  regulation and  function as a  first  step  to inhibiting its expression  or activity. However, a second repression mechanism has recently been shown to be mediated by the transcription factor  ZBTB7A/LRF,  suggesting  that  understanding  the  regulation  of  ZBTB7A  may  also  be useful.  Here  we  show  that  KLF1  directly  drives  expression  of  ZBTB7A in  erythroid  cells  by binding  to  its  proximal  promoter.  We  have  also  uncovered  an  erythroid-specific  regulation   mechanism,  leading  to  the upregulation  of  a  novel  ZBTB7A transcript  in  the  erythroid compartment.  The  demonstration that  ZBTB7A,  like  BCL11A, is  a  KLF1  target  gene  also  fits with  the  observation  that  reduced KLF1  expression  or  activity  is  associated  with  HbF  derepression. Overall design: ChIP-seq was undetaken in duplicate on two different cell lines against KLF1. Input controls were inncluded