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Molecular and Cellular Biology Volume 33, 2013 - Issue 15
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Article

Generation of Mice Deficient in both KLF3/BKLF and KLF8 Reveals a Genetic Interaction and a Role for These Factors in Embryonic Globin Gene Silencing

Alister P. W. Funnella School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
,
Ka Sin Maka School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
,
Natalie A. Twinea School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
,
Gregory J. Pelkab Children's Medical Research Institute, Westmead, New South Wales, Australia
,
Laura J. Nortona School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
,
Tania Radziewicb Children's Medical Research Institute, Westmead, New South Wales, Australia
,
Melinda Powerb Children's Medical Research Institute, Westmead, New South Wales, Australia
,
Marc R. Wilkinsa School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
,
Kim S. Bell-Andersonc School of Molecular Bioscience, University of Sydney, Sydney, New South Wales, Australia
,
Stuart T. Fraserd Disciplines of Physiology, Anatomy and Histology, School of Medical Science, University of Sydney, Sydney, New South Wales, Australia
,
Andrew C. Perkinse Mater Medical Research Institute, Translational Research Institute, Woolloongabba, Queensland, Australia;f Division of Molecular Genetics and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland, Australia
,
Patrick P. Tamb Children's Medical Research Institute, Westmead, New South Wales, Australia
,
Richard C. M. Pearsona School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, Australia
&
Merlin Crossleya School of Biotechnology and Biomolecular Sciences, University of New South Wales, Sydney, New South Wales, AustraliaCorrespondence[email protected]
 show all
Pages 2976-2987 | Received 17 Jan 2013, Accepted 19 May 2013, Published online: 20 Mar 2023
 
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Abstract

Krüppel-like factors 3 and 8 (KLF3 and KLF8) are highly related transcriptional regulators that bind to similar sequences of DNA. We have previously shown that in erythroid cells there is a regulatory hierarchy within the KLF family, whereby KLF1 drives the expression of both the Klf3 and Klf8 genes and KLF3 in turn represses Klf8 expression. While the erythroid roles of KLF1 and KLF3 have been explored, the contribution of KLF8 to this regulatory network has been unknown. To investigate this, we have generated a mouse model with disrupted KLF8 expression. While these mice are viable, albeit with a reduced life span, mice lacking both KLF3 and KLF8 die at around embryonic day 14.5 (E14.5), indicative of a genetic interaction between these two factors. In the fetal liver, Klf3 Klf8 double mutant embryos exhibit greater dysregulation of gene expression than either of the two single mutants. In particular, we observe derepression of embryonic, but not adult, globin expression. Taken together, these results suggest that KLF3 and KLF8 have overlapping roles in vivo and participate in the silencing of embryonic globin expression during development.

SUPPLEMENTAL MATERIAL

Supplemental material for this article may be found at http://dx.doi.org/10.1128/MCB.00074-13.

ACKNOWLEDGMENTS

This work is supported by funding from the National Health and Medical Research Council and the Australian Research Council.

Authorship contributions are as follows. A.P.W.F. designed and performed research, analyzed data, and wrote the paper. K.S.M., L.J.N., G.J.P., T.R., and M.P. performed research and analyzed data. N.A.T., M.R.W., and K.S.B.-A. analyzed data. S.T.F., A.C.P., and P.P.T. designed research and analyzed data. R.C.M.P. designed research, analyzed data, and wrote the paper. M.C. devised the concept and research, analyzed data, and wrote the paper.

We declare that no competing financial interests exist.

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