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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.
- Source :
-
Molecular and cellular biology [Mol Cell Biol] 2013 Aug; Vol. 33 (15), pp. 2976-87. Date of Electronic Publication: 2013 May 28. - Publication Year :
- 2013
-
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.
- Subjects :
- Animals
COS Cells
Chlorocebus aethiops
Female
Gene Silencing
Kruppel-Like Transcription Factors metabolism
Liver embryology
Liver metabolism
Male
Mice genetics
Mice, Inbred C57BL
Transcription Factors metabolism
Gene Expression Regulation, Developmental
Globins genetics
Kruppel-Like Transcription Factors genetics
Mice embryology
Transcription Factors genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5549
- Volume :
- 33
- Issue :
- 15
- Database :
- MEDLINE
- Journal :
- Molecular and cellular biology
- Publication Type :
- Academic Journal
- Accession number :
- 23716600
- Full Text :
- https://doi.org/10.1128/MCB.00074-13