BCL11A represses HBG transcription in K562 cells.
BCL11A on chromosome 2p16 was recently shown to be a major quantitative trait locus for Hb F level and F-cell number in several populations with or without beta-hemoglobinopathy. We now show that BCL11A isoforms are expressed in K562 cells. Butyrate induction of HBG globin production in K562 is associated with reduced BCL11A. Conversely, augmented expression of BCL11A in K562 cells through transfection of BCL11A expression vector results in more than 50% reduction of HBG promoter transcription activity. This transcription repression can be abrogated by sodium butyrate. BCL11A binds to GGCCGG motif in nucleotide -56 to -51 on the HBG proximal promoter. Together, these data are consistent with BCL11A being able to bind to a core motif in the HBG proximal promoter, recruit and interact with partners to form a repression complex, leading to deacetylation of histones and down-regulation of the HBG transcription.
Chen
Zhiyi
Z
Center of Excellence in Sickle Cell Disease, Division of Hematology/Oncology, Department of Medicine, Boston University School of Medicine, Boston, MA 02118, USA.
Luo
Hong-yuan
HY
Steinberg
Martin H
MH
Chui
David H K
DH
D001665:Binding Sites; D002087:Butyrates / Q000494:pharmacology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D018628:Gene Dosage; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D020014:K562 Cells / Q000187:drug effects / Q000378:metabolism; D016297:Mutagenesis, Site-Directed; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000502:physiology; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects; D055545:gamma-Globins / Q000096:biosynthesis* / Q000235:genetics
C486563:BCL11A protein, human; D002087:Butyrates; D002352:Carrier Proteins; D006877:Hydroxamic Acids; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; D055545:gamma-Globins; C012589:trichostatin A