The transcription factor KLF11 can induce gamma-globin gene expression in the setting of in vivo adult erythropoiesis.
Previous studies in a fetal erythroid cell line demonstrated that the transcription factor, Krüppel-like factor 11 (KLF11), could specifically induce transcription from a gamma-globin gene promoter, and that this induction was mediated through a specific canonical CACCC cis-DNA binding motif. We report here that ectopic expression of KLF11 can also induce fetal gamma-globin gene expression in the setting of adult erythropoiesis both in vitro and in vivo. Studies in an adult-stage murine erythroleukemia (MEL) cell line demonstrated that retrovirus vector-mediated transduction of KLF11 could increase both the amount of expression from a basally active, but not from a overtly silenced, recombinant gamma-globin transgene, as well as the frequency of cells expressing this transgene. A similar pattern of gamma-globin gene induction was also observed both in vitro and in vivo following KLF11 transduction of bone marrow from mice containing a basally active gamma-globin transgene. These studies provide the first evidence that ectopic expression of a transcription factor can induce gamma-globin gene expression in vivo during adult erythropoiesis.
Emery
David W
DW
University of Washington Department of Medicine, Division of Medical Genetics, Seattle, WA 98195-7720, USA. demery@u.washington.edu
Gavriilidis
Georgios
G
Asano
Haruhiko
H
Stamatoyannopoulos
George
G
D000818:Animals; D016026:Bone Marrow Transplantation; D002460:Cell Line; D015672:Erythroid Precursor Cells / Q000166:cytology / Q000378:metabolism; D004920:Erythropoiesis / Q000235:genetics*; D005434:Flow Cytometry; D015870:Gene Expression; D005914:Globins / Q000235:genetics* / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D041681:NIH 3T3 Cells; D012190:Retroviridae / Q000235:genetics; D013997:Time Factors; D014162:Transfection
D051741:Kruppel-Like Transcription Factors; D049452:Green Fluorescent Proteins; D005914:Globins