Specific activation of human beta-Globin gene expression by the transcription factor Ikaros

Perkins, Andrew C., Papathanasiou, Peter, Goodnow, Christopher C. and Keys, Janelle R. (2005). Specific activation of human beta-Globin gene expression by the transcription factor Ikaros. In: Blood. Proceedings of: ASH Annual Meeting Abstracts. 47th ASH Annual Meeting, Atlanta, GA, USA, (1013A-1014A). 10-13 December 2005.


Author Perkins, Andrew C.
Papathanasiou, Peter
Goodnow, Christopher C.
Keys, Janelle R.
Title of paper Specific activation of human beta-Globin gene expression by the transcription factor Ikaros
Conference name 47th ASH Annual Meeting
Conference location Atlanta, GA, USA
Conference dates 10-13 December 2005
Proceedings title Blood. Proceedings of: ASH Annual Meeting Abstracts   Check publisher's open access policy
Journal name Blood   Check publisher's open access policy
Place of Publication Washington, D.C., USA
Publisher American Society of Hematology
Publication Year 2005
Sub-type Poster
ISSN 0006-4971
1528-0020
Volume 106
Issue 11
Start page 1013A
End page 1014A
Total pages 1
Language eng
Abstract/Summary The zinc finger transcription factor Ikaros is recognized as a key regulator of lymphocyte differentiation. Recently generated dominant negative mutants have hinted at a broader role in haematopoietic stem cell generation. Most recently, a mouse strain, IkarosPlastic, with a point mutation in Ikaros that disrupts DNA binding but preserves efficient assembly of Ikaros protein complexes, is embryonically lethal due to severe defects in erythrocyte differentiation (Papathanasiou P, et al,. Immunity, 2003). (1). These mice display normal murine globin gene expression in the fetal liver. However in humans the globin locus is under alternative regulatory control, particularly with respect to the fetal-to-adult globin switch. Thus, to determine if Ikaros plays a role in human globin switching we crossed the IkarosPlastic mice with mice transgenic for a YAC containing the entire human b-globin locus, which show human fetal to adult globin gene switching from E12 to E17. Embryos were harvested from E12.5 to E15.5 and globin expression was determined in the fetal liver by real-time PCR (relative to actin). At all time points human gamma-globin gene expression was not significantly altered by the presence of the IkarosPlastic mutatation (relative expression Ikaroswt/wt 1±0.11, IkarosPlastic/Plastic 0.82±0.12). In contrast, human beta-globin gene expression was significantly down-regulated in IkarosPlastic fetal livers (relative expression Ikaroswt/wt 1±0.14, IkarosPlastic/Plastic 0.18±0.07). Interestingly, neither murine a- or b-globin gene expression was significantly different to wild type mice, which suggests that the transcription factor Ikaros plays a specific role in the transcriptional activation of the human b-globin gene during development. The mechanism by which this occurs remains to be elucidated, however it is intriguing to consider that Ikaros may act as a potentiator of transcription for erythroid specific transcription factors such as EKLF. Experiments to address this will be presented.
Subjects 1103 Clinical Sciences
Q-Index Code EX
Q-Index Status Provisional Code
Institutional Status Unknown
Additional Notes Abstract number: 3641

 
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Created: Thu, 04 Mar 2010, 15:43:18 EST by Laura McTaggart on behalf of Institute for Molecular Bioscience