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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. 33:2976-2987
- Publication Year :
- 2013
- Publisher :
- Informa UK Limited, 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 :
- Male
Mutant
Kruppel-Like Transcription Factors
KLF1
Biology
Mice
Chlorocebus aethiops
Gene expression
Animals
Gene silencing
Gene Silencing
Globin
Molecular Biology
Transcription factor
Gene
Genetics
Gene Expression Regulation, Developmental
Articles
Cell Biology
Globins
Mice, Inbred C57BL
Liver
COS Cells
KLF3
Female
Transcription Factors
Subjects
Details
- ISSN :
- 10985549
- Volume :
- 33
- Database :
- OpenAIRE
- Journal :
- Molecular and Cellular Biology
- Accession number :
- edsair.doi.dedup.....cbe9b7a1a84623c6005940415f274dfb